Special Issue "The Role of Integrins in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 April 2019)

Special Issue Editors

Guest Editor
Prof. Dr. Johannes Eble

Westfälische Wilhelms-Universität Münster, Institute of Physiological Chemistry and Pathobiochemistry, Münster, Germany
Website 1 | Website 2 | E-Mail
Interests: integrins, extracellular matrix, cell-matrix interactions, snake venom-derived integrin inhibitors, redox biology
Guest Editor
Prof. Dr. Donald Gullberg

Universitetet i Bergen, Department of Biomedicine and Centre of Cancer Biomarkers (CCBIO), Bergen, Norway
Website | E-Mail
Interests: integrins, extracellualr matrix, collagens, fibroblasts, tissue fibrosis, tumor fibrosis

Special Issue Information

Dear Colleagues,

In recent years, our understanding of the molecular events in solid tumors has increased and undergone several dogma shifts. Instead of focusing solely on the mutations, and the effects of these on the inner life of carcinoma cells, the realization has dawned that, for a tumor to grow and spread, the interactions of tumor cells with the tumor microenvironment and the non-tumor cells residing in the tumor milieu are of utmost importance. Current focus in the field concerns the roles of the extracellular matrix, immune cells, cancer associated fibroblasts and vascular cells in creating a permissive environment for tumor growth, tumor spread and chemoresistance.

In the current issue, we will focus on the role of integrins in cancer cells, on immune cells, in cancer-associated fibroblasts and on vascular cells, to orchestrate the events contributing to tumorigenesis and metastasis.

Prof. Dr. Johannes Eble
Prof. Dr. Donald Gullberg
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular mechanism integrins
  • tumor microenvironment
  • tumor stroma
  • cell–matrix interactions

Published Papers (3 papers)

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Research

Open AccessArticle Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
Cancers 2019, 11(4), 587; https://doi.org/10.3390/cancers11040587
Received: 22 March 2019 / Revised: 18 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
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Abstract
New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 [...] Read more.
New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody–drug conjugate (ADC), an integrin α10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin α10β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM. Full article
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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Open AccessArticle Efficacy of a Selective Binder of αVβ3 Integrin Linked to the Tyrosine Kinase Inhibitor Sunitinib in Ovarian Carcinoma Preclinical Models
Cancers 2019, 11(4), 531; https://doi.org/10.3390/cancers11040531
Received: 28 March 2019 / Accepted: 11 April 2019 / Published: 13 April 2019
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Abstract
Ovarian carcinoma, the most lethal gynecological cancer, is characterized by late diagnosis, with drug resistance limiting the efficacy of platinum-based therapy. Since some integrins are upregulated in cancer, including ovarian carcinoma, they represent a potential target for drug delivery. Receptor tyrosine kinases are [...] Read more.
Ovarian carcinoma, the most lethal gynecological cancer, is characterized by late diagnosis, with drug resistance limiting the efficacy of platinum-based therapy. Since some integrins are upregulated in cancer, including ovarian carcinoma, they represent a potential target for drug delivery. Receptor tyrosine kinases are also deregulated in cancer and their expression has been associated with drug resistance. Here, the antitumor effects of three conjugates possessing a selective binder of the extracellular portion of integrin αVβ3 covalently linked to the tyrosine kinase inhibitor sunitinib were investigated in cisplatin-sensitive and -resistant ovarian carcinoma cells expressing both tyrosine kinase VEGFR2 and αVβ3 at different levels. We found that one of the three compounds was active in inhibiting the growth of both drug-sensitive and -resistant cells in the micromolar range with a slightly increased potency in resistant cells as compared to sunitinib. The same compound markedly impaired cell migratory and invasive abilities and reduced paxillin phosphorylation. Antitumor activity studies in IGROV-1/Pt1 cells xenografted in nude mice revealed a striking activity of this conjugate versus sunitinib. Taken together, our results support the interest of integrin-targeted sunitinib conjugates for the treatment of drug-resistant tumors. Full article
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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Open AccessArticle The Interaction between Laminin-332 and α3β1 Integrin Determines Differentiation and Maintenance of CAFs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells
Received: 26 October 2018 / Revised: 3 December 2018 / Accepted: 18 December 2018 / Published: 21 December 2018
Cited by 1 | PDF Full-text (3127 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming [...] Read more.
Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming growth factor-β (TGF-β), and stromal matrix proteins, such as laminin-332, are factors which promote CAF differentiation. In a spheroid culture system, differentiation of CAFs was analysed for laminin-332 production, laminin-binding integrin repertoire, adhesion and migration behaviour, and, in heterospheroids, for their interplay with the pancreatic duct adenocarcinoma AsPC-I cells. Our data reveal that CAFs produce laminin-332 thus contributing to its ectopic deposition within the tumour stroma. Moreover, CAF differentiation correlates with an increased expression of α3β1 integrin, the principal laminin-332-receptor. Beyond its role as novel CAF marker protein, integrin α3β1 crucially determines differentiation and maintenance of the CAF phenotype, as knock-out of the integrin α3 subunit reversed the CAF differentiated state. AsPC-I cells co-cultured in heterospheroids with integrin α3-deficient CAFs invaded less than from heterospheroids with wild-type CAFs. This study highlights the role of integrin α3β1 integrin-laminin-332 interaction of CAFs which promotes and sustains differentiation of CAFs and promotes carcinoma invasion. Full article
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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