Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis

Huang, Yen-Lin and Liang, Ching-Yeu and Ritz, Danilo and Coelho, Ricardo and Septiadi, Dedy and Estermann, Manuela and Cumin, Cécile and Rimmer, Natalie and Schötzau, Andreas and Núñez López, Mónica and Fedier, André and Konantz, Martina and Vlajnic, Tatjana and Calabrese, Diego and Lengerke, Claudia and David, Leonor and Rothen-Rutishauser, Barbara and Jacob, Francis and Heinzelmann-Schwarz, Viola. (2020) Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis. eLife, 9. e59442.

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Official URL: https://edoc.unibas.ch/80782/

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The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin
UniBasel Contributors:Konantz, Martina
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Jun 2021 13:33
Deposited On:09 Jun 2021 13:33

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