CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma
Abstract
:1. Introduction
2. Results
2.1. CD147 was Overexpressed on Malignant T Cells in MF/SS
2.2. Cyclophilin A Was Expressed on Epidermal Keratinocytes and Malignant T Cells in MF/SS
2.3. Serum CypA Levels Were Increased and Correlated with Disease Severity Markers in MF/SS Patients
2.4. CD147-CypA Interactions Promote Proliferation of CTCL Cell Lines through the Phosphorylation of Extracellular Signal-Regulated Kinase 1/2 and Akt
3. Discussion
4. Materials and Methods
4.1. Patients and Tissue Samples
4.2. Cell Lines
4.3. RNA Isolation and Quantitative Reverse Transcription-PCR
4.4. Immunohistochemistry
4.5. Flow Cytometric Analyses
4.6. Enzyme-Linked Immunosorbent Assay
4.7. Proliferation Assays by Cell Count
4.8. Western Blotting
4.9. In vivo Animal Experiments
4.10. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Willemze, R.; Jaffe, E.S.; Burg, G.; Cerroni, L.; Berti, E.; Swerdlow, S.H.; Ralfkiaer, E.; Chimenti, S.; Diaz-Perez, J.L.; Duncan, L.M.; et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005, 105, 3768–3785. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohtsuka, M.; Hamada, T.; Miyagaki, T.; Shimauchi, T.; Yonekura, K.; Kiyohara, E.; Fujita, H.; Izutsu, K.; Okuma, K.; Kawai, K.; et al. Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020. J. Dermatol. 2021, 48, e49–e71. [Google Scholar] [CrossRef]
- Nicolay, J.P.; Albrecht, J.D.; Alberti-Violetti, S.; Berti, E. CCR4 in cutaneous T-cell lymphoma: Therapeutic targeting of a pathogenic driver. Eur. J. Immunol. 2021. Online ahead of print. [Google Scholar] [CrossRef]
- Scarisbrick, J.J.; Prince, H.M.; Vermeer, M.H.; Quaglino, P.; Horwitz, S.; Porcu, P.; Stadler, R.; Wood, G.S.; Beylot-Barry, M.; Pham-Ledard, A.; et al. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J. Clin. Oncol. 2015, 33, 3766–3773. [Google Scholar] [CrossRef] [PubMed]
- Oka, T.; Miyagaki, T. Novel and Future Therapeutic Drugs for Advanced Mycosis Fungoides and Sézary Syndrome. Front. Med. 2019, 6, 116. [Google Scholar] [CrossRef] [PubMed]
- Kamijo, H.; Miyagaki, T. Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy. Curr. Treat. Options Oncol. 2021, 22, 10. [Google Scholar] [CrossRef]
- Geskin, L.J.; Viragova, S.; Stolz, D.B.; Fuschiotti, P. Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation. Blood 2015, 125, 2798–2805. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kamijo, H.; Miyagaki, T.; Shishido-Takahashi, N.; Nakajima, R.; Oka, T.; Suga, H.; Sugaya, M.; Sato, S. Aberrant CD137 ligand expression induced by GATA6 overexpression promotes tumor progression in cutaneous T-cell lymphoma. Blood 2018, 132, 1922–1935. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, H.; Boki, H.; Kamijo, H.; Nakajima, R.; Oka, T.; Shishido-Takahashi, N.; Suga, H.; Sugaya, M.; Sato, S.; Miyagaki, T. YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways. J. Investig. Dermatol. 2020, 140, 860–868.e3. [Google Scholar] [CrossRef]
- Kamijo, H.; Miyagaki, T.; Takahashi-Shishido, N.; Nakajima, R.; Oka, T.; Suga, H.; Sugaya, M.; Sato, S. Thrombospondin-1 promotes tumor progression in cutaneous T-cell lymphoma via CD47. Leukemia 2020, 34, 845–856. [Google Scholar] [CrossRef]
- Boki, H.; Miyagaki, T.; Shono, Y.; Kamijo, H.; Oka, T.; Suga, H.; Asano, Y.; Sugaya, M.; Sato, S. Increased Expression of Delta-like Ligand 4 in Mycosis Fungoides. Acta Derm. Venereol. 2020, 100, adv00059. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miyauchi, T.; Kanekura, T.; Yamaoka, A.; Ozawa, M.; Miyazawa, S.; Muramatsu, T. Basigin, a new, broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin V domain and the beta-chain of major histocompatibility complex class II antigen. J. Biochem. 1990, 107, 316–323. [Google Scholar] [CrossRef]
- Biswas, C.; Zhang, Y.; DeCastro, R.; Guo, H.; Nakamura, T.; Kataoka, H.; Nabeshima, K. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995, 55, 434–439. [Google Scholar] [PubMed]
- Grass, G.D.; Toole, B.P. How, with whom and when: An overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity. Biosci. Rep. 2015, 36, e00283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Landras, A.; Reger de Moura, C.; Jouenne, F.; Lebbe, C.; Menashi, S.; Mourah, S. CD147 is a promising target of tumor progression and a prognostic biomarker. Cancers 2019, 11, 1803. [Google Scholar] [CrossRef] [Green Version]
- Xin, X.; Zeng, X.; Gu, H.; Li, M.; Tan, H.; Jin, Z.; Hua, T.; Shi, R.; Wang, H. CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis. Sci. Rep. 2016, 6, 32804. [Google Scholar] [CrossRef] [Green Version]
- Fu, J.; Fu, J.; Chen, X.; Zhang, Y.; Gu, H.; Bai, Y. CD147 and VEGF co-expression predicts prognosis in patients with acute myeloid leukemia. Jpn. J. Clin. Oncol. 2010, 40, 1046–1052. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arendt, B.K.; Walters, D.K.; Wu, X.; Tschumper, R.C.; Huddleston, P.M.; Henderson, K.J.; Dispenzieri, A.; Jelinek, D.F. Increased expression of extracellular matrix metalloproteinase inducer (CD147) in multiple myeloma: Role in regulation of myeloma cell proliferation. Leukemia 2012, 26, 2286–2296. [Google Scholar] [CrossRef] [Green Version]
- Thorns, C.; Feller, A.C.; Merz, H. EMMPRIN (CD 147) is expressed in Hodgkin’s lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases. Anticancer Res. 2002, 22, 1983–1986. [Google Scholar] [PubMed]
- Nabeshima, K.; Suzumiya, J.; Nagano, M.; Ohshima, K.; Toole, B.P.; Tamura, K.; Iwasaki, H.; Kikuchi, M. Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas. J. Pathol. 2004, 202, 341–351. [Google Scholar] [CrossRef]
- Panchabhai, S.; Schlam, I.; Sebastian, S.; Fonseca, R. PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma. Leukemia 2017, 31, 991–994. [Google Scholar] [CrossRef] [PubMed]
- Handschumacher, R.E.; Harding, M.W.; Rice, J.; Drugge, R.J.; Speicher, D.W. Cyclophilin: A specific cytosolic binding protein for cyclosporin A. Science 1984, 226, 544–547. [Google Scholar] [CrossRef]
- Wang, P.; Heitman, J. The cyclophilins. Genome Biol. 2005, 6, 226. [Google Scholar] [CrossRef] [Green Version]
- Obchoei, S.; Wongkhan, S.; Wongkham, C.; Li, M.; Yao, Q.; Chen, C. Cyclophilin A: Potential functions and therapeutic target for human cancer. Med. Sci. Monit. 2009, 15, RA221–RA232. [Google Scholar]
- Li, M.; Zhai, Q.; Bharadwaj, U.; Wang, H.; Li, F.; Fisher, W.E.; Chen, C.; Yao, Q. Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. Cancer 2006, 106, 2284–2294. [Google Scholar] [CrossRef]
- Takahashi, M.; Suzuki, S.; Ishikawa, K. Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma. Oncol. Rep. 2012, 27, 198–203. [Google Scholar]
- Obchoei, S.; Sawanyawisuth, K.; Wongkham, C.; Kasinrerk, W.; Yao, Q.; Chen, C.; Wongkham, S. Secreted cyclophilin A mediates G1/S phase transition of cholangiocarcinoma cells via CD147/ERK1/2 pathway. Tumour Biol. 2015, 36, 849–859. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Hu, C.; Xiao, Z.; Luo, C.; Liu, Z. Downregulation of CyclophilinA/CD147 Axis Induces Cell Apoptosis and Inhibits Glioma Aggressiveness. BioMed Res. Int. 2020, 2020, 7035847. [Google Scholar]
- Zhu, D.; Wang, Z.; Zhao, J.J.; Calimeri, T.; Meng, J.; Hideshima, T.; Fulciniti, M.; Kang, Y.; Ficarro, S.B.; Tai, Y.T.; et al. The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat. Med. 2015, 21, 572–580. [Google Scholar] [CrossRef]
- Krejsgaard, T.; Kopp, K.; Ralfkiaer, E.; Willumsgaard, A.E.; Eriksen, K.W.; Labuda, T.; Rasmussen, S.; Mathiesen, A.M.; Geisler, C.; Lauenborg, B.; et al. A novel xenograft model of cutaneous T-cell lymphoma. Exp. Dermatol. 2010, 19, 1096–1102. [Google Scholar] [CrossRef] [PubMed]
- Zhang, R.Y.; Wei, D.; Liu, Z.K.; Yong, Y.L.; Wei, W.; Zhang, Z.Y.; Lv, J.J.; Zhang, Z.; Chen, Z.N.; Bian, H. Biodistribution and localization of iodine-131-labeled metuximab in patients with hepatocellular carcinoma. Cancer. Biol. Ther. 2006, 5, 318–322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bian, H.; Zheng, J.S.; Nan, G.; Li, R.; Chen, C.; Hu, C.X.; Zhang, Y.; Sun, B.; Wang, X.L.; Cui, S.C.; et al. Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation. J. Natl. Cancer. Inst. 2014, 106, dju239. [Google Scholar] [CrossRef] [Green Version]
- Tseng, H.C.; Xiong, W.; Badeti, S.; Yang, Y.; Ma, M.; Liu, T.; Ramos, C.A.; Dotti, G.; Fritzky, L.; Jiang, J.G.; et al. Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma. Nat. Commun. 2020, 11, 4810. [Google Scholar] [CrossRef]
- Feng, M.X.; Li, J.P.; Wang, H.; Shen, Y.X.; Tan, L.J.; Wang, Q.; Wang, Y.Q. Clinical significance of cyclophilin a expression in esophageal squamous cell carcinoma. Genet. Test. Mol. Biomark. 2015, 19, 182–186. [Google Scholar] [CrossRef]
- Li, H.; Jiang, C.; Wu, D.; Shi, S.; Liao, M.; Wang, J.; Li, Y.; Xu, Z. The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis. PLoS ONE 2017, 12, e0180271. [Google Scholar] [CrossRef] [Green Version]
- Xiao, W.; Zhao, S.; Shen, F.; Liang, J.; Chen, J. Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma. Exp. Ther. Med. 2017, 14, 2637–2642. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; Li, M.; Xing, L.; Yu, J. High expression level of peptidylprolyl isomerase A is correlated with poor prognosis of liver hepatocellular carcinoma. Oncol. Lett. 2019, 18, 4691–4702. [Google Scholar] [CrossRef] [PubMed]
- Caudron, A.; Battistella, M.; Feugeas, J.P.; Pages, C.; Basset-Seguin, N.; Mazouz, D.S.; Funck, B.E.; Sadoux, A.; Podgorniak, M.P.; Menashi, S.; et al. EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma. Exp. Dermatol. 2016, 25, 618–622. [Google Scholar] [CrossRef] [PubMed]
- Al-Daraji, W.I.; Grant, K.R.; Ryan, K.; Saxton, A.; Reynolds, N.J. Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J. Investig. Dermatol. 2002, 118, 779–788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, J.M.; Sohng, J.K.; Lee, W.H.; Oh, T.J.; Jung, H.J. Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells. Int. J. Mol. Sci. 2021, 22, 2473. [Google Scholar] [CrossRef] [PubMed]
- Mao, X.; Orchard, G.; Mitchell, T.J.; Oyama, N.; Russell-Jones, R.; Vermeer, M.H.; Willemze, R.; van Doorn, R.; Tensen, C.P.; Young, B.D.; et al. A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: Evidence for dysregulated expression of JUNB and JUND in MF and SS. J. Cutan. Pathol. 2008, 35, 899–910. [Google Scholar] [CrossRef] [PubMed]
- Levidou, G.; Siakantaris, M.; Papadaki, T.; Papadavid, E.; Vassilakopoulos, T.P.; Angelopoulou, M.K.; Marinos, L.; Nikolaou, V.; Economidi, A.; Antoniou, C.; et al. A comprehensive immunohistochemical approach of AKT/mTOR pathway and p-STAT3 in mycosis fungoides. J. Am. Acad. Dermatol. 2013, 69, 375–384. [Google Scholar] [CrossRef] [PubMed]
- Papadavid, E.; Korkolopoulou, P.; Levidou, G.; Saetta, A.A.; Papadaki, T.; Siakantaris, M.; Nikolaou, V.; Oikonomidi, A.; Chatziandreou, I.; Marinos, L.; et al. In situ assessment of PI3K and PTEN alterations in mycosis fungoides: Correlation with clinicopathological features. Exp. Dermatol. 2014, 23, 931–933. [Google Scholar] [CrossRef] [PubMed]
- Park, J.; Yang, J.; Wenzel, A.T.; Ramachandran, A.; Lee, W.J.; Daniels, J.C.; Kim, J.; Martinez-Escala, E.; Amankulor, N.; Pro, B.; et al. Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E). Blood 2017, 130, 1430–1440. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 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 (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sakamoto, M.; Miyagaki, T.; Kamijo, H.; Oka, T.; Boki, H.; Takahashi-Shishido, N.; Suga, H.; Sugaya, M.; Sato, S. CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma. Int. J. Mol. Sci. 2021, 22, 7889. https://doi.org/10.3390/ijms22157889
Sakamoto M, Miyagaki T, Kamijo H, Oka T, Boki H, Takahashi-Shishido N, Suga H, Sugaya M, Sato S. CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma. International Journal of Molecular Sciences. 2021; 22(15):7889. https://doi.org/10.3390/ijms22157889
Chicago/Turabian StyleSakamoto, Minami, Tomomitsu Miyagaki, Hiroaki Kamijo, Tomonori Oka, Hikari Boki, Naomi Takahashi-Shishido, Hiraku Suga, Makoto Sugaya, and Shinichi Sato. 2021. "CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma" International Journal of Molecular Sciences 22, no. 15: 7889. https://doi.org/10.3390/ijms22157889