RGD-Binding Integrins in Head and Neck Cancers
Abstract
:1. Introduction
2. Integrins in HNSCC
2.1. The αv Integrin Subfamily
2.1.1. αvβ3 and αvβ5 Integrins
2.1.2. αvβ6
2.1.3. αvβ8
2.2. The β1 Integrin Subfamily
α5β1
2.3. αIIbβ3
3. Applications of Integrin-Targeted Agents
3.1. Imaging
3.2. Targeted Therapeutic Delivery
3.3. Antitumour and Anti-Metastatic Agents
4. Conclusions
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015, 65, 87–108. [Google Scholar] [CrossRef] [PubMed]
- Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017, 3, 524–548. [Google Scholar]
- GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016, 388, 1459–1544. [Google Scholar]
- Walden, M.J.; Aygun, N. Head and neck cancer. Semin. Roentgenol. 2013, 48, 75–86. [Google Scholar] [CrossRef] [PubMed]
- Neville, B.W.; Day, T.A. Oral cancer and precancerous lesions. CA Cancer J. Clin. 2002, 52, 195–215. [Google Scholar] [CrossRef] [PubMed]
- Adelstein, D.J.; Li, Y.; Adams, G.L.; Wagner, H., Jr.; Kish, J.A.; Ensley, J.F.; Schuller, D.E.; Forastiere, A.A. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J. Clin. Oncol. 2003, 21, 92–98. [Google Scholar] [CrossRef] [PubMed]
- Bourhis, J.; Sire, C.; Graff, P.; Gregoire, V.; Maingon, P.; Calais, G.; Gery, B.; Martin, L.; Alfonsi, M.; Desprez, P.; et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): An open-label phase 3 randomised trial. Lancet Oncol. 2012, 13, 145–153. [Google Scholar] [CrossRef]
- Calais, G.; Bardet, E.; Sire, C.; Alfonsi, M.; Bourhis, J.; Rhein, B.; Tortochaux, J.; Man, Y.T.; Auvray, H.; Garaud, P. Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98–02 GORTEC Phase II trial. Int. J. Radiat. Oncol. Biol. Phys. 2004, 58, 161–166. [Google Scholar] [CrossRef]
- Denis, F.; Garaud, P.; Bardet, E.; Alfonsi, M.; Sire, C.; Germain, T.; Bergerot, P.; Rhein, B.; Tortochaux, J.; Calais, G. Final results of the 94–01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J. Clin. Oncol. 2004, 22, 69–76. [Google Scholar] [CrossRef] [PubMed]
- Ang, K.K.; Zhang, Q.; Rosenthal, D.I.; Nguyen-Tan, P.F.; Sherman, E.J.; Weber, R.S.; Galvin, J.M.; Bonner, J.A.; Harris, J.; El-Naggar, A.K.; et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J. Clin. Oncol. 2014, 32, 2940–2950. [Google Scholar] [CrossRef] [PubMed]
- Giralt, J.; Trigo, J.; Nuyts, S.; Ozsahin, M.; Skladowski, K.; Hatoum, G.; Daisne, J.F.; Yunes Ancona, A.C.; Cmelak, A.; Mesia, R.; et al. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): A randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015, 16, 221–232. [Google Scholar] [CrossRef]
- Cox, D.; Brennan, M.; Moran, N. Integrins as therapeutic targets: Lessons and opportunities. Nat. Rev. Drug Discov. 2010, 9, 804–820. [Google Scholar] [CrossRef] [PubMed]
- Campbell, I.D.; Humphries, M.J. Integrin structure, activation, and interactions. Cold Spring Harb. Perspect. Biol. 2011, 3, a004994. [Google Scholar] [CrossRef] [PubMed]
- Hohenester, E. Signalling complexes at the cell-matrix interface. Curr. Opin. Struct. Biol. 2014, 29, 10–16. [Google Scholar] [CrossRef] [PubMed]
- Shimaoka, M.; Takagi, J.; Springer, T.A. Conformational regulation of integrin structure and function. Annu. Rev. Biophys. Biomol. Struct. 2002, 31, 485–516. [Google Scholar] [CrossRef] [PubMed]
- Hynes, R.O. Integrins: Bidirectional, allosteric signaling machines. Cell 2002, 110, 673–687. [Google Scholar] [CrossRef]
- Avraamides, C.J.; Garmy-Susini, B.; Varner, J.A. Integrins in angiogenesis and lymphangiogenesis. Nat. Rev. Cancer 2008, 8, 604–617. [Google Scholar] [CrossRef] [PubMed]
- Goodman, S.L.; Picard, M. Integrins as therapeutic targets. Trends Pharmacol. Sci. 2012, 33, 405–412. [Google Scholar] [CrossRef] [PubMed]
- Goswami, S. Importance of integrin receptors in the field of pharmaceutical & medical science. ABC 2013, 3, 224–252. [Google Scholar]
- Millard, M.; Odde, S.; Neamati, N. Integrin Targeted Therapeutics. Theranostics 2011, 1, 154–188. [Google Scholar] [CrossRef] [PubMed]
- Ley, K.; Rivera-Nieves, J.; Sandborn, W.J.; Shattil, S. Integrin-based therapeutics: Biological basis, clinical use and new drugs. Nat. Rev. Drug Discov. 2016, 15, 173–183. [Google Scholar] [CrossRef] [PubMed]
- Bianconi, D.; Unseld, M.; Prager, G.W. Integrins in the Spotlight of Cancer. Int. J. Mol. Sci. 2016, 17, 2037. [Google Scholar] [CrossRef] [PubMed]
- Silva, R.; D’Amico, G.; Hodivala-Dilke, K.M.; Reynolds, L.E. Integrins: The Keys to Unlocking Angiogenesis. Arterioscler. Thromb. Vasc. Biol. 2008, 28, 1703–1713. [Google Scholar] [CrossRef] [PubMed]
- Weis, S.M.; Cheresh, D.A. Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat. Med. 2011, 17, 1359–1370. [Google Scholar] [CrossRef] [PubMed]
- Atkinson, S.J.; Ellison, T.S.; Steri, V.; Gould, E.; Robinson, S.D. Redefining the role(s) of endothelial αvβ3-integrin in angiogenesis. Biochem. Soc. Trans. 2014, 42, 1590–1595. [Google Scholar] [CrossRef] [PubMed]
- Worthington, J.J.; Klementowicz, J.E.; Travis, M.A. TGFb: A sleeping giant awoken by integrins. Trends Biochem. Sci. 2011, 36, 47–54. [Google Scholar] [CrossRef] [PubMed]
- Ozawa, A.; Sato, Y.; Imabayashi, T.; Uemura, T.; Takagi, J.; Sekiguchi, K. Molecular Basis of the Ligand-binding Specificity of αvβ8 Integrin. J. Biol. Chem. 2016, 291, 11551–11565. [Google Scholar] [CrossRef] [PubMed]
- Cambier, S.; Gline, S.; Mu, D.; Collins, R.; Araya, J.; Dolganov, G.; Einheber, S.; Boudreau, N.; Nishimura, S.L. Integrin αvβ8-mediated activation of transforming growth factor-β by perivascular astrocytes: An angiogenic control switch. Am. J. Pathol. 2005, 166, 1883–1894. [Google Scholar] [CrossRef]
- Bianchi, A.; Gervasi, M.E.; Bakin, A. Role of β5-integrin in epithelial-mesenchymal transition in response to TGF-β. Cell Cycle 2010, 9, 1647–1659. [Google Scholar] [CrossRef] [PubMed]
- Bandyopadhyay, A.; Raghavan, S. Defining the Role of Integrin αvβ6 in Cancer. Curr. Drug Targets 2009, 10, 645–652. [Google Scholar] [CrossRef] [PubMed]
- Dutta, A.; Li, J.; Lu, H.; Akech, J.; Pratap, J.; Wang, T.; Zerlanko, B.J.; Fitzgerald, T.J.; Jiang, Z.; Birbe, R.; et al. Integrin αvβ6 promotes an osteolytic program in cancer cells by upregulating MMP2. Cancer Res. 2014, 74, 1598–1608. [Google Scholar] [CrossRef] [PubMed]
- Lamar, J.M.; Pumiglia, K.M.; DiPersio, C.M. An Immortalization-Dependent Switch in Integrin Function Up-regulates MMP-9 to Enhance Tumor Cell Invasion. Cancer Res. 2008, 68, 7371–7379. [Google Scholar] [CrossRef] [PubMed]
- Cantor, D.I.; Cheruku, H.R.; Nice, E.C.; Baker, M.S. Integrin αvβ6 sets the stage for colorectal cancer metastasis. Cancer Metastasis Rev. 2015, 34, 715–734. [Google Scholar] [CrossRef] [PubMed]
- Brooks, S.A.; Lomax-Browne, H.J.; Carter, T.M.; Kinch, C.E.; Hall, D.M.S. Molecular interactions in cancer cell metastasis. Acta Histochem. 2009, 112, 3–25. [Google Scholar] [CrossRef] [PubMed]
- Staflin, K.; Krueger, J.S.; Hachmann, J.; Forsyth, J.S.; Lorger, M.; Steiniger, S.C.J.; Mee, J.; Pop, C.; Salvesen, G.S.; Janda, K.D.; et al. Targeting activated integrin αvβ3 with patient-derived antibodies impacts late-stage multiorgan metastasis. Clin. Exp. Metastasis 2010, 27, 217–231. [Google Scholar] [CrossRef] [PubMed]
- Van der Horst, G.; van den Hoogen, C.; Buijs, J.T.; Cheung, H.; Bloys, H.; Pelger, R.C.M.; Lorenzon, G.; Heckmann, B.; Feyen, J.; Pujuguet, P.; et al. Targeting of av-Integrins in Stem/Progenitor Cells and Supportive Microenvironment Impairs Bone Metastasis in Human Prostate Cancer. Neoplasia 2011, 13, 516–525. [Google Scholar] [CrossRef] [PubMed]
- Sutherland, M.; Gordon, A.; Shnyder, S.D.; Patterson, L.H.; Sheldrake, H.M. RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis. Cancers (Basel) 2012, 4, 1106–1145. [Google Scholar] [CrossRef] [PubMed]
- Sheldrake, H.M.; Patterson, L.H. Function and antagonism of β3 integrins in the development of cancer therapy. Curr. Cancer Drug Targets 2009, 9, 519–540. [Google Scholar] [CrossRef] [PubMed]
- Brennan, M.; Cox, D. The therapeutic potential of I-domain integrins. Adv. Exp. Med. Biol. 2014, 819, 157–178. [Google Scholar] [PubMed]
- Sheldrake, H.M.; Patterson, L.H. Strategies to inhibit tumor associated integrin receptors: Rationale for dual and multi-antagonists. J. Med. Chem. 2014, 57, 6301–6315. [Google Scholar] [CrossRef] [PubMed]
- Hamidi, H.; Pietila, M.; Ivaska, J. The complexity of integrins in cancer and new scopes for therapeutic targeting. Br. J. Cancer 2016, 115, 1017–1023. [Google Scholar] [CrossRef] [PubMed]
- Georgolios, A.K.; Batistatou, A.; Charalabopoulos, K. Integrins in head and neck squamous cell carcinoma (HNSCC): A review of the current literature. Cell Commun. Adhes. 2005, 12, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Fabricius, E.M.; Wildner, G.P.; Kruse-Boitschenko, U.; Hoffmeister, B.; Goodman, S.L.; Raguse, J.D. Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas. Exp. Ther. Med. 2011, 2, 9–19. [Google Scholar] [CrossRef] [PubMed]
- Jones, J.; Watt, F.M.; Speight, P.M. Changes in the expression of αv integrins in oral squamous cell carcinomas. J. Oral. Pathol. Med. 1997, 26, 63–68. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Liu, Y.; Kan, X.; Li, Y.; Liu, M.; Lu, J.G. Elevated expression of integrin αv and β5 subunit in laryngeal squamous-cell carcinoma associated with lymphatic metastasis and angiogenesis. Pathol. Res. Pract. 2013, 209, 105–109. [Google Scholar] [CrossRef] [PubMed]
- Li, P.; Liu, F.; Sun, L.; Zhao, Z.; Ding, X.; Shang, D.; Xu, Z.; Sun, C. Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3. Int. J. Mol. Med. 2011, 27, 679–687. [Google Scholar] [PubMed]
- Vitolo, D.; Ciocci, L.; Ferrauti, P.; Cicerone, E.; Gallo, A.; De Vincentiis, M.; Baroni, C.D. α5 integrin distribution and TGFβ1 gene expression in supraglottic carcinoma: Their role in neoplastic local invasion and metastasis. Head Neck 2000, 22, 48–56. [Google Scholar] [CrossRef]
- Shinohara, M.; Nakamura, S.; Sasaki, M.; Kurahara, S.; Ikebe, T.; Harada, T.; Shirasuna, K. Expression of integrins in squamous cell carcinoma of the oral cavity. Correlations with tumor invasion and metastasis. Am. J. Clin. Pathol. 1999, 111, 75–88. [Google Scholar] [CrossRef] [PubMed]
- Brooks, P.C. Requirement of Vascular Integrin alphaVbeta3 for Angiogenesis. Science 1994, 264, 569–571. [Google Scholar] [CrossRef] [PubMed]
- Nisato, R.E.; Tille, J.C.; Jonczyk, A.; Goodman, S.L.; Pepper, M.S. αvβ3 and αvβ5 integrin antagonists inhibit angiogenesis in vitro. Angiogenesis 2003, 6, 105–119. [Google Scholar] [CrossRef] [PubMed]
- Miller, S.E.; Veale, R.B. Environmental modulation of α(v), α(2) and β(1) integrin subunit expression in human oesophageal squamous cell carcinomas. Cell. Biol. Int. 2001, 25, 61–69. [Google Scholar] [CrossRef] [PubMed]
- Hayashido, Y.; Kitano, H.; Sakaue, T.; Fujii, T.; Suematsu, M.; Sakurai, S.; Okamoto, T. Overexpression of integrin αv facilitates proliferation and invasion of oral squamous cell carcinoma cells via MEK/ERK signaling pathway that is activated by interaction of integrin αvβ8 with type I collagen. Int. J. Oncol. 2014, 45, 1875–1882. [Google Scholar] [PubMed]
- Lu, J.G.; Li, Y.; Li, L.; Kan, X. Overexpression of osteopontin and integrin αv in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis. J. Cancer Res. Clin. Oncol. 2011, 137, 1613–1618. [Google Scholar] [CrossRef] [PubMed]
- Xuan, S.-H.; Zhou, Y.-G.; Pan, J.-Q.; Zhu, W.; Xu, P. Overexpression of integrin αv in the human nasopharyngeal carcinoma associated with metastasis and progression. Cancer Biomark. 2013, 13, 323–328. [Google Scholar] [CrossRef] [PubMed]
- Ou, J.; Luan, W.; Deng, J.; Sa, R.; Liang, H. αV integrin induces multicellular radioresistance in human nasopharyngeal carcinoma via activating SAPK/JNK pathway. PLoS ONE 2012, 7, e38737. [Google Scholar] [CrossRef] [PubMed]
- Lu, J.G.; Sun, Y.N.; Wang, C.; Jin de, J.; Liu, M. Role of the αv-integrin subunit in cell proliferation, apoptosis and tumor metastasis of laryngeal and hypopharyngeal squamous cell carcinomas: A clinical and in vitro investigation. Eur. Arch. Oto-Rhino-Laryngol. 2009, 266, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Kurokawa, A.; Nagata, M.; Kitamura, N.; Noman, A.A.; Ohnishi, M.; Ohyama, T.; Kobayashi, T.; Shingaki, S.; Takagi, R.; Oral Maxillofacial Pathology and Surgery Group. Diagnostic value of integrin α3, β4, and β5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma. Cancer 2008, 112, 1272–1281. [Google Scholar] [CrossRef] [PubMed]
- Stojanovic, N.; Brozovic, A.; Majhen, D.; Bosnar, M.H.; Fritz, G.; Osmak, M.; Ambriovic-Ristov, A. Integrin αvβ3 expression in tongue squamous carcinoma cells Cal27 confers anticancer drug resistance through loss of pSrc(Y418). Biochim. Biophys. Acta 2016, 1863, 1969–1978. [Google Scholar] [CrossRef] [PubMed]
- Jones, J.; Sugiyama, M.; Speight, P.M.; Watt, F.M. Restoration of αvβ5 integrin expression in neoplastic keratinocytes results in increased capacity for terminal differentiation and suppression of anchorage-independent growth. Oncogene 1996, 12, 119–126. [Google Scholar] [PubMed]
- Janes, S.M.; Watt, F.M. Switch from αvβ5 to αvβ6 integrin expression protects squamous cell carcinomas from anoikis. J. Cell. Biol. 2004, 166, 419–431. [Google Scholar] [CrossRef] [PubMed]
- Brooks, P.C.; Montgomery, A.M.; Rosenfeld, M.; Reisfeld, R.A.; Hu, T.; Klier, G.; Cheresh, D.A. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994, 79, 1157–1164. [Google Scholar] [CrossRef]
- Max, R.; Gerritsen, R.R.; Nooijen, P.T.; Goodman, S.L.; Sutter, A.; Keilholz, U.; Ruiter, D.J.; De Waal, R.M. Immunohistochemical analysis of integrin αvβ3 expression on tumor-associated vessels of human carcinomas. Int. J. Cancer 1997, 71, 320–324. [Google Scholar] [CrossRef]
- Terry, S.Y.; Abiraj, K.; Frielink, C.; van Dijk, L.K.; Bussink, J.; Oyen, W.J.; Boerman, O.C. Imaging integrin αvβ3 on blood vessels with 111In-RGD2 in head and neck tumor xenografts. J. Nucl. Med. 2014, 55, 281–286. [Google Scholar] [CrossRef] [PubMed]
- Beer, A.J.; Grosu, A.L.; Carlsen, J.; Kolk, A.; Sarbia, M.; Stangier, I.; Watzlowik, P.; Wester, H.J.; Haubner, R.; Schwaiger, M. [18F]galacto-RGD positron emission tomography for imaging of αvβ3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin. Cancer Res. 2007, 13, 6610–6616. [Google Scholar] [CrossRef] [PubMed]
- Qin, X.; Yan, M.; Zhang, J.; Wang, X.; Shen, Z.; Lv, Z.; Li, Z.; Wei, W.; Chen, W. TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis. Sci. Rep. 2016, 6, 20587. [Google Scholar] [CrossRef] [PubMed]
- Kumar, C.C.; Malkowski, M.; Yin, Z.; Tanghetti, E.; Yaremko, B.; Nechuta, T.; Varner, J.; Liu, M.; Smith, E.M.; Neustadt, B.; et al. Inhibition of angiogenesis and tumor growth by SCH221153, a dual αvβ3 and αvβ5 integrin receptor antagonist. Cancer Res. 2001, 61, 2232–2238. [Google Scholar] [PubMed]
- Beekman, K.W.; Colevas, A.D.; Cooney, K.; Dipaola, R.; Dunn, R.L.; Gross, M.; Keller, E.T.; Pienta, K.J.; Ryan, C.J.; Smith, D.; et al. Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: Scientific rationale and study design. Clin. Genitourin. Cancer 2006, 4, 299–302. [Google Scholar] [CrossRef] [PubMed]
- Ruffini, F.; Graziani, G.; Levati, L.; Tentori, L.; D’Atri, S.; Lacal, P.M. Cilengitide downmodulates invasiveness and vasculogenic mimicry of neuropilin 1 expressing melanoma cells through the inhibition of αvβ5 integrin. Int. J. Cancer 2015, 136, E545–E558. [Google Scholar] [CrossRef] [PubMed]
- Stupp, R.; Hegi, M.E.; Neyns, B.; Goldbrunner, R.; Schlegel, U.; Clement, P.M.; Grabenbauer, G.G.; Ochsenbein, A.F.; Simon, M.; Dietrich, P.Y.; et al. Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 2010, 28, 2712–2718. [Google Scholar] [CrossRef] [PubMed]
- Stupp, R.; Hegi, M.E.; Gorlia, T.; Erridge, S.C.; Perry, J.; Hong, Y.K.; Aldape, K.D.; Lhermitte, B.; Pietsch, T.; Grujicic, D.; et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014, 15, 1100–1108. [Google Scholar] [CrossRef]
- Raguse, J.D.; Gath, H.J.; Bier, J.; Riess, H.; Oettle, H. Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour. Oral Oncol. 2004, 40, 228–230. [Google Scholar] [CrossRef] [PubMed]
- Vermorken, J.B.; Guigay, J.; Mesia, R.; Trigo, J.M.; Keilholz, U.; Kerber, A.; Bethe, U.; Picard, M.; Brummendorf, T.H. Phase I/II trial of cilengitide with cetuximab, cisplatin and 5-fluorouracil in recurrent and/or metastatic squamous cell cancer of the head and neck: Findings of the phase I part. Br. J. Cancer 2011, 104, 1691–1696. [Google Scholar] [CrossRef] [PubMed]
- Vermorken, J.B.; Peyrade, F.; Krauss, J.; Mesia, R.; Remenar, E.; Gauler, T.C.; Keilholz, U.; Delord, J.P.; Schafhausen, P.; Erfan, J.; et al. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: Results of the randomized phase I/II ADVANTAGE trial (phase II part). Ann. Oncol. 2014, 25, 682–688. [Google Scholar] [CrossRef] [PubMed]
- Heiduschka, G.; Lill, C.; Schneider, S.; Seemann, R.; Kornek, G.; Schmid, R.; Kotowski, U.; Thurnher, D. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines. Strahlenther. Onkol. 2014, 190, 472–479. [Google Scholar] [CrossRef] [PubMed]
- Wichmann, G.; Korner, C.; Boehm, A.; Mozet, C.; Dietz, A. Stimulation by Monocyte Chemoattractant Protein-1 Modulates the Ex Vivo Colony Formation by Head and Neck Squamous Cell Carcinoma Cells. Anticancer Res. 2015, 35, 3917–3924. [Google Scholar] [PubMed]
- Wichmann, G.; Cedra, S.; Schlegel, D.; Kolb, M.; Wiegand, S.; Boehm, A.; Hofer, M.; Dietz, A. Cilengitide and Cetuximab Reduce Cytokine Production and Colony Formation of Head and Neck Squamous Cell Carcinoma Cells Ex Vivo. Anticancer Res. 2017, 37, 521–527. [Google Scholar] [CrossRef] [PubMed]
- Franovic, A.; Elliott, K.C.; Seguin, L.; Camargo, M.F.; Weis, S.M.; Cheresh, D.A. Glioblastomas require integrin αvβ3/PAK4 signaling to escape senescence. Cancer Res. 2015, 75, 4466–4473. [Google Scholar] [CrossRef] [PubMed]
- Becker, A.; von Richter, O.; Kovar, A.; Scheible, H.; van Lier, J.J.; Johne, A. Metabolism and disposition of the αv-integrin αvβ3/αvβ5 receptor antagonist cilengitide, a cyclic polypeptide, in humans. J. Clin. Pharmacol. 2015, 55, 815–824. [Google Scholar] [CrossRef] [PubMed]
- Cirkel, G.A.; Milojkovic Kerklaan, B.; Vanhoutte, F.; Van der Aa, A.; Lorenzon, G.; Namour, F.; Pujuguet, P.; Darquenne, S.; de Vos, F.Y.F.; Snijders, T.J.; et al. A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies. Investig. New Drugs 2016, 34, 184–192. [Google Scholar] [CrossRef] [PubMed]
- Hsiao, J.R.; Chang, Y.; Chen, Y.L.; Hsieh, S.H.; Hsu, K.F.; Wang, C.F.; Tsai, S.T.; Jin, Y.T. Cyclic αvβ6-targeting peptide selected from biopanning with clinical potential for head and neck squamous cell carcinoma. Head Neck 2010, 32, 160–172. [Google Scholar] [CrossRef] [PubMed]
- Ramos, D.M.; Chen, B.L.; Boylen, K.; Stern, M.; Kramer, R.H.; Sheppard, D.; Nishimura, S.L.; Greenspan, D.; Zardi, L.; Pytela, R. Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C. Int. J. Cancer 1997, 72, 369–376. [Google Scholar] [CrossRef]
- Eriksen, J.G.; Steiniche, T.; Sogaard, H.; Overgaard, J. Expression of integrins and E-cadherin in squamous cell carcinomas of the head and neck. APMIS 2004, 112, 560–568. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Liang, B.; Gao, H.; Zhang, F.; Wang, B.; Dong, X.; Niu, J. Integrin αvβ6 as a novel marker for diagnosis and metastatic potential of thyroid carcinoma. Head Neck Oncol. 2013, 5, 7. [Google Scholar]
- Ramos, D.M.; But, M.; Regezi, J.; Schmidt, B.L.; Atakilit, A.; Dang, D.; Ellis, D.; Jordan, R.; Li, X. Expression of integrin β6 enhances invasive behavior in oral squamous cell carcinoma. Matrix Biol. 2002, 21, 297–307. [Google Scholar] [CrossRef]
- Larjava, H.; Haapasalmi, K.; Salo, T.; Wiebe, C.; Uitto, V.J. Keratinocyte integrins in wound healing and chronic inflammation of the human periodontium. Oral Dis. 1996, 2, 77–86. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.; Lee, C.; Lee, S.; Siu, A.; Ramos, D.M. The cytoplasmic extension of the integrin β6 subunit regulates epithelial-to-mesenchymal transition. Anticancer Res. 2014, 34, 659–664. [Google Scholar] [PubMed]
- Ramos, D.M.; Dang, D.; Sadler, S. The role of the integrin αvβ6 in regulating the epithelial to mesenchymal transition in oral cancer. Anticancer Res. 2009, 29, 125–130. [Google Scholar] [PubMed]
- Xue, H.; Atakilit, A.; Zhu, W.; Li, X.; Ramos, D.M.; Pytela, R. Role of the αvβ6 integrin in human oral squamous cell carcinoma growth in vivo and in vitro. Biochem. Biophys. Res. Commun. 2001, 288, 610–618. [Google Scholar] [CrossRef] [PubMed]
- Koivisto, L.; Grenman, R.; Heino, J.; Larjava, H. Integrins α5β1, αvβ1, and αvβ6collaborate in squamous carcinoma cell spreading and migration on fibronectin. Exp. Cell Res. 2000, 255, 10–17. [Google Scholar] [CrossRef] [PubMed]
- Reed, N.I.; Tang, Y.Z.; McIntosh, J.; Wu, Y.; Molnar, K.S.; Civitavecchia, A.; Sheppard, D.; DeGrado, W.F.; Jo, H. Exploring N-Arylsulfonyl-l-proline Scaffold as a Platform for Potent and Selective αvβ1 Integrin Inhibitors. ACS Med. Chem. Lett. 2016, 7, 902–907. [Google Scholar] [CrossRef] [PubMed]
- Reed, N.I.; Jo, H.; Chen, C.; Tsujino, K.; Arnold, T.D.; DeGrado, W.F.; Sheppard, D. The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. Sci. Transl. Med. 2015, 7, 288ra79. [Google Scholar] [CrossRef] [PubMed]
- Adams, J.; Anderson, E.C.; Blackham, E.E.; Chiu, Y.W.R.; Clarke, T.; Eccles, N.; Gill, L.A.; Haye, J.J.; Haywood, H.T.; Hoenig, C.R.; et al. Structure Activity Relationships of αv Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents. ACS Med. Chem. Lett. 2014, 5, 1207–1212. [Google Scholar] [CrossRef] [PubMed]
- Goodman, S.L.; Holzemann, G.; Sulyok, G.A.G.; Kessler, H. Nanomolar Small Molecule Inhibitors for αnβ6, αnβ5, and αnβ3 Integrins. J. Med. Chem. 2002, 45, 1045–1051. [Google Scholar] [CrossRef] [PubMed]
- Ni, R.; Shen, X.; Wu, H.; Zhu, W.; Ni, J.; Huang, Z.; Song, Y.; Gao, X. Expression and significance of integrins subunits in laryngeal squamous cell carcinoma. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2010, 24, 686–689. [Google Scholar] [PubMed]
- Wang, D.; Muller, S.; Amin, A.R.; Huang, D.; Su, L.; Hu, Z.; Rahman, M.A.; Nannapaneni, S.; Koenig, L.; Chen, Z.; et al. The pivotal role of integrin β1 in metastasis of head and neck squamous cell carcinoma. Clin. Cancer Res. 2012, 18, 4589–4599. [Google Scholar] [CrossRef] [PubMed]
- De Moraes, F.P.; Lourenço, S.V.; Ianez, R.C.; de Sousa, E.A.; Silva, M.M.; Damascena, A.S.; Kowalski, L.P.; Soares, F.A.; Coutinho-Camillo, C.M. Expression of stem cell markers in oral cavity and oropharynx squamous cell carcinoma. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2017, 123, 113–122. [Google Scholar] [CrossRef] [PubMed]
- Yen, Y.C.; Hsiao, J.R.; Jiang, S.S.; Chang, J.S.; Wang, S.H.; Shen, Y.Y.; Chen, C.H.; Chang, I.S.; Chang, J.Y.; Chen, Y.W. Insulin-like growth factor-independent insulin-like growth factor binding protein 3 promotes cell migration and lymph node metastasis of oral squamous cell carcinoma cells by requirement of integrin β1. Oncotarget 2015, 6, 41837–41855. [Google Scholar] [CrossRef] [PubMed]
- Koukourakis, M.I.; Giatromanolaki, A.; Tsakmaki, V.; Danielidis, V.; Sivridis, E. Cancer stem cell phenotype relates to radio-chemotherapy outcome in locally advanced squamous cell head-neck cancer. Br. J. Cancer 2012, 106, 846–853. [Google Scholar] [CrossRef] [PubMed]
- Bragado, P.; Estrada, Y.; Sosa, M.S.; Avivar-Valderas, A.; Cannan, D.; Genden, E.; Teng, M.; Ranganathan, A.C.; Wen, H.C.; Kapoor, A.; et al. Analysis of marker-defined HNSCC subpopulations reveals a dynamic regulation of tumor initiating properties. PLoS ONE 2012, 7, e29974. [Google Scholar] [CrossRef] [PubMed]
- Ming, X.Y.; Fu, L.; Zhang, L.Y.; Qin, Y.R.; Cao, T.T.; Chan, K.W.; Ma, S.; Xie, D.; Guan, X.Y. Integrin α7 is a functional cancer stem cell surface marker in oesophageal squamous cell carcinoma. Nat. Commun. 2016, 7, 13568. [Google Scholar] [CrossRef] [PubMed]
- Eke, I.; Deuse, Y.; Hehlgans, S.; Gurtner, K.; Krause, M.; Baumann, M.; Shevchenko, A.; Sandfort, V.; Cordes, N. β(1)Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J. Clin. Investig. 2012, 122, 1529–1540. [Google Scholar] [CrossRef] [PubMed]
- Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M.A.; Cordes, N. Targeting of β1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells. Oncogene 2016, 35, 1353–1362. [Google Scholar] [CrossRef] [PubMed]
- Eke, I.; Zscheppang, K.; Dickreuter, E.; Hickmann, L.; Mazzeo, E.; Unger, K.; Krause, M.; Cordes, N. Simultaneous β1 integrin-EGFR targeting and radiosensitization of human head and neck cancer. J. Natl. Cancer Inst. 2015, 107, dju419. [Google Scholar] [CrossRef] [PubMed]
- Parajuli, H.; Teh, M.T.; Abrahamsen, S.; Christoffersen, I.; Neppelberg, E.; Lybak, S.; Osman, T.; Johannessen, A.C.; Gullberg, D.; Skarstein, K.; et al. Integrin α11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression. J. Oral Pathol. Med. 2016, 46, 267–275. [Google Scholar] [CrossRef] [PubMed]
- Steglich, A.; Vehlow, A.; Eke, I.; Cordes, N. α integrin targeting for radiosensitization of three-dimensionally grown human head and neck squamous cell carcinoma cells. Cancer Lett. 2015, 357, 542–548. [Google Scholar] [CrossRef] [PubMed]
- Xie, J.J.; Guo, J.C.; Wu, Z.Y.; Xu, X.E.; Wu, J.Y.; Chen, B.; Ran, L.Q.; Liao, L.D.; Li, E.M.; Xu, L.Y. Integrin α5 promotes tumor progression and is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma. Hum. Pathol. 2016, 48, 69–75. [Google Scholar] [CrossRef] [PubMed]
- Jung, A.C.; Ray, A.M.; Ramolu, L.; Macabre, C.; Simon, F.; Noulet, F.; Blandin, A.F.; Renner, G.; Lehmann, M.; Choulier, L.; et al. Caveolin-1-negative head and neck squamous cell carcinoma primary tumors display increased epithelial to mesenchymal transition and prometastatic properties. Oncotarget 2015, 6, 41884–41901. [Google Scholar] [PubMed]
- Cianfrocca, M.E.; Kimmel, K.A.; Gallo, J.; Cardoso, T.; Brown, M.M.; Hudes, G.; Lewis, N.; Weiner, L.; Lam, G.N.; Brown, S.C.; et al. Phase 1 Trial of the Antiangiogenic Peptide ATN-161 (Ac-PHSCN-NH2), a beta Integrin Antagonist, in Patients with Solid Tumours. Br. J. Cancer 2006, 94, 1621–1626. [Google Scholar] [CrossRef] [PubMed]
- Barkan, D.; Chambers, A.F. β1-integrin: A Potential Therapeutic Target in the Battle against Cancer Recurrence. Clin. Cancer Res. 2011, 17, 7219–7223. [Google Scholar] [CrossRef] [PubMed]
- Lonsdorf, A.S.; Kramer, B.F.; Fahrleitner, M.; Schonberger, T.; Gnerlich, S.; Ring, S.; Gehring, S.; Schneider, S.W.; Kruhlak, M.J.; Meuth, S.G.; et al. Engagement of αIIbβ3 (GPIIb/IIIa) with αvβ3 integrin mediates interaction of melanoma cells with platelets: A connection to hematogenous metastasis. J. Biol. Chem. 2012, 287, 2168–2178. [Google Scholar] [CrossRef] [PubMed]
- Parikka, M.; Nissinen, L.; Kainulainen, T.; Bruckner-Tuderman, L.; Salo, T.; Heino, J.; Tasanen, K. Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration—A novel role for αIIβ integrin and tirofiban. Exp. Cell Res. 2006, 312, 1431–1438. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.W.; Chen, J.K.; Wang, J.S. Exercise affects platelet-promoted tumor cell adhesion and invasion to endothelium. Eur. J. Appl. Physiol. 2009, 105, 393–401. [Google Scholar] [CrossRef] [PubMed]
- Bornstein, S.; Schmidt, M.; Choonoo, G.; Levin, T.; Gray, J.; Thomas, C.R.; Wong, M.; McWeeney, S. IL-10 and integrin signaling pathways are associated with head and neck cancer progression. BMC Genom. 2016, 17, 38. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Wang, F. Development of RGD-based radiotracers for tumor imaging and therapy: Translating from bench to bedside. Curr. Mol. Med. 2013, 13, 1487–1505. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Yu, L.; Wang, X.; Zhang, X.; Liu, M.; Zeng, W. Integrin (αvβ3) Targeted RGD Peptide Based Probe for Cancer Optical Imaging. Curr. Protein Pept. Sci. 2016, 17, 570–581. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Wu, Y.; Wang, F.; Liu, Z. Molecular imaging of integrin αvβ6 expression in living subjects. Am. J. Nucl. Med. Mol. Imaging 2014, 4, 333–345. [Google Scholar] [PubMed]
- Nothelfer, E.M.; Zitzmann-Kolbe, S.; Garcia-Boy, R.; Kramer, S.; Herold-Mende, C.; Altmann, A.; Eisenhut, M.; Mier, W.; Haberkorn, U. Identification and characterization of a peptide with affinity to head and neck cancer. J. Nucl. Med. 2009, 50, 426–434. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Zhang, Y.; Hong, K.; Zhu, S.; Wan, J. Photoacoustic and Fluorescence Imaging of Cutaneous Squamous Cell Carcinoma in Living Subjects Using a Probe Targeting Integrin αvβ6. Sci. Rep. 2017, 7, 42442. [Google Scholar] [CrossRef] [PubMed]
- Liu, S. Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins. Bioconj. Chem. 2015, 26, 1413–1438. [Google Scholar] [CrossRef] [PubMed]
- Beer, A.J.; Haubner, R.; Sarbia, M.; Goebel, M.; Luderschmidt, S.; Grosu, A.L.; Schnell, O.; Niemeyer, M.; Kessler, H.; Wester, H.J.; et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin αvβ3 expression in man. Clin. Cancer Res. 2006, 12, 3942–3949. [Google Scholar] [CrossRef] [PubMed]
- Beer, A.J.; Lorenzen, S.; Metz, S.; Herrmann, K.; Watzlowik, P.; Wester, H.J.; Peschel, C.; Lordick, F.; Schwaiger, M. Comparison of integrin αvβ3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: A PET study using 18F-galacto-RGD and 18F-FDG. J. Nucl. Med. 2008, 49, 22–29. [Google Scholar] [CrossRef] [PubMed]
- Huang, H.; Bai, Y.L.; Yang, K.; Tang, H.; Wang, Y.W. Optical imaging of head and neck squamous cell carcinoma in vivo using arginine-glycine-aspartic acid peptide conjugated near-infrared quantum dots. OncoTargets Ther 2013, 6, 1779–1787. [Google Scholar]
- Atallah, I.; Milet, C.; Henry, M.; Josserand, V.; Reyt, E.; Coll, J.L.; Hurbin, A.; Righini, C. Near-infrared fluorescence imaging-guided surgery improves recurrence-free survival rate in novel orthotopic animal model of head and neck squamous cell carcinoma. Head Neck 2016, 38, E246–E255. [Google Scholar] [CrossRef] [PubMed]
- Atallah, I.; Milet, C.; Quatre, R.; Henry, M.; Reyt, E.; Coll, J.L.; Hurbin, A.; Righini, C.A. Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC. Eur. Ann. Oto-Rhino-Laryngol. Head Neck Dis. 2015, 132, 337–342. [Google Scholar] [CrossRef] [PubMed]
- Arosio, D.; Casagrande, C. Advancement in integrin facilitated drug delivery. Adv. Drug Deliv. Rev. 2016, 97, 111–143. [Google Scholar] [CrossRef] [PubMed]
- Katsamakas, S.; Chatzisideri, T.; Thysiadis, S.; Sarli, V. RGD-mediated delivery of small-molecule drugs. Future Med. Chem. 2017, 9, 579–604. [Google Scholar] [CrossRef] [PubMed]
- Dissanayake, S.; Denny, W.A.; Gamage, S.; Sarojini, V. Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides. J. Control. Release 2017, 250, 62–76. [Google Scholar] [CrossRef] [PubMed]
- Spitaleri, A.; Mari, S.; Curnis, F.; Traversari, C.; Longhi, R.; Bordignon, C.; Corti, A.; Rizzardi, G.-P.; Musco, G. Structural basis for the interaction of isoDGR with the RGD-binding site of αnβ3 integrin. J. Biol. Chem. 2008, 283, 19757–19768. [Google Scholar] [CrossRef] [PubMed]
- Tambet, T.; Sugahara, K.N.; Ruoslahti, E. Tumor-penetrating peptides. Front. Oncol. 2013, 3, 216. [Google Scholar]
- Crisp, J.L.; Savariar, E.N.; Glasgow, H.L.; Ellies, L.G.; Whitney, M.A.; Tsien, R.Y. Dual targeting of integrin αvβ3 and matrix metalloproteinase-2 for optical imaging of tumors and chemotherapeutic delivery. Mol. Cancer Ther. 2014, 13, 1514–1525. [Google Scholar] [CrossRef] [PubMed]
- Buckel, L.; Savariar, E.N.; Crisp, J.L.; Jones, K.A.; Hicks, A.M.; Scanderbeg, D.J.; Nguyen, Q.T.; Sicklick, J.K.; Lowy, A.M.; Tsien, R.Y.; et al. Tumor radiosensitization by monomethyl auristatin E: Mechanism of action and targeted delivery. Cancer Res. 2015, 75, 1376–1387. [Google Scholar] [CrossRef] [PubMed]
- Hauff, S.J.; Raju, S.C.; Orosco, R.K.; Gross, A.M.; Diaz-Perez, J.A.; Savariar, E.; Nashi, N.; Hasselman, J.; Whitney, M.; Myers, J.N.; et al. Matrix-metalloproteinases in head and neck carcinoma-cancer genome atlas analysis and fluorescence imaging in mice. Otolaryngol. Head Neck Surg. 2014, 151, 612–618. [Google Scholar] [CrossRef] [PubMed]
- Xie, H.; Diagaradjane, P.; Deorukhkar, A.A.; Goins, B.; Bao, A.; Phillips, W.T.; Wang, Z.; Schwartz, J.; Krishnan, S. Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy. Int. J. Nanomed. 2011, 6, 259–269. [Google Scholar] [CrossRef] [PubMed]
- Wang, D.; Fei, B.; Halig, L.V.; Qin, X.; Hu, Z.; Xu, H.; Wang, Y.A.; Chen, Z.; Kim, S.; Shin, D.M.; et al. Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer. ACS Nano 2014, 8, 6620–6632. [Google Scholar] [CrossRef] [PubMed]
- Halig, L.V.; Wang, D.; Wang, A.Y.; Chen, Z.G.; Fei, B. Biodistribution Study of Nanoparticle Encapsulated Photodynamic Therapy Drugs Using Multispectral Imaging. Proc. SPIE Int. Soc. Opt. Eng. 2013, 8672. [Google Scholar] [CrossRef]
- Kim, D.H.; Vitol, E.A.; Liu, J.; Balasubramanian, S.; Gosztola, D.J.; Cohen, E.E.; Novosad, V.; Rozhkova, E.A. Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles. Langmuir 2013, 29, 7425–7432. [Google Scholar] [CrossRef] [PubMed]
- Eberlein, C.; Kendrew, J.; McDaid, K.; Alfred, A.; Kang, J.S.; Jacobs, V.N.; Ross, S.J.; Rooney, C.; Smith, N.R.; Rinkenberger, J.; et al. A human monoclonal antibody 264RAD targeting αvβ6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo. Oncogene 2013, 32, 4406–4416. [Google Scholar] [CrossRef] [PubMed]
- Howard, M.J.; Dicara, D.; Marshall, J.F. αvβ6 Peptide Ligands and Their Uses. U.S. Patent 8383593 B2, 3 October 2006. [Google Scholar]
- Bakewell, S.J.; Nestor, P.; Prasad, S.; Tomasson, M.H.; Dowland, N.; Mehrotra, M.; Scarborough, R.M.; Kanter, J.; Abe, K.; Phillips, D.; et al. Platelet and Osteoclast β3 Integrins are Critical for Bone Metastasis. Proc. Natl. Acad. Sci. USA 2003, 100, 14205–14210. [Google Scholar] [CrossRef] [PubMed]
- Trikha, M.; Zhou, Z.; Timar, J.; Raso, E.; Kennel, M.; Emmell, E.; Nakada, M. Multiple Roles for Platelet GPIIb/IIIa and αvβ3 Integrins in Tumor Growth, Angiogenesis, and Metastasis. Cancer Res. 2002, 62, 2824–2833. [Google Scholar] [PubMed]
- Buergy, D.; WEnz, F.; Groden, C.; Brockmann, M.A. Tumor-platelet interaction in solid tumors. Int. J. Cancer 2012, 130, 2747–2760. [Google Scholar] [CrossRef] [PubMed]
- Weber, M.R.; Zuka, M.; Lorger, M.; Tschan, M.; Torbett, B.E.; Zijlstra, A.; Quigley, J.P.; Staflin, K.; Eliceiri, B.P.; Krueger, J.S.; et al. Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream. Thromb. Res. 2016, 140, S27–S36. [Google Scholar] [CrossRef]
- Echtler, K.; Konrad, I.; Lorenz, M.; Schneider, S.; Hofmaier, S.; Plenagl, F.; Stark, K.; Czermak, T.; Tirniceriu, A.; Eichhorn, M.; et al. Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis. PLoS ONE 2017, 12, e0172788. [Google Scholar] [CrossRef] [PubMed]
Integrin | SE | SCC | E | S | Ref |
---|---|---|---|---|---|
αvβ3 | −/+ | −/+ | ++ | + | [43] |
αvβ3 | − | [44] | |||
αvβ3 | + | −/+ | [45] | ||
αvβ3 | −/+ | +++ | [46] | ||
αvβ5 | + | ++ | ++ | +++ | [43] |
αvβ5 | + | +++ | [45] | ||
αvβ5 | + | ++ | ++ | [44] | |
αvβ1 | +++ | +++ | [45] | ||
αvβ6 | − | ++ | n/a | [44] | |
αvβ6 | ++ | +++ | [45] | ||
αvβ8 | +++ | +++ | [45] | ||
αIIbβ3 | |||||
α5β1 | + | ++ | + | ++ | [43] |
α5β1 | − | +++ | [47] | ||
α5β1 | −/+ | ++ | [48] |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ahmedah, H.T.; Patterson, L.H.; Shnyder, S.D.; Sheldrake, H.M. RGD-Binding Integrins in Head and Neck Cancers. Cancers 2017, 9, 56. https://doi.org/10.3390/cancers9060056
Ahmedah HT, Patterson LH, Shnyder SD, Sheldrake HM. RGD-Binding Integrins in Head and Neck Cancers. Cancers. 2017; 9(6):56. https://doi.org/10.3390/cancers9060056
Chicago/Turabian StyleAhmedah, Hanadi Talal, Laurence H. Patterson, Steven D. Shnyder, and Helen M. Sheldrake. 2017. "RGD-Binding Integrins in Head and Neck Cancers" Cancers 9, no. 6: 56. https://doi.org/10.3390/cancers9060056