Collagen-rich omentum is a premetastatic niche for integrin alpha 2-mediated peritoneal metastasis

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Huang, YL (Author) Other; Liang, CY (Author) Other; Ritz, D (Author) Other; Coelho, R (Author) Other; Septiadi, D (Author) Other; Estermann, M (Author) Other; Cumin, C (Author) Other; Rimmer, N (Author) Other; Schotzau, A (Author) Other; Lopez, MN (Author) Other; Fedier, A (Author) Other; Konantz, M (Author) Other; Vlajnic, T (Author) Other; Calabrese, D (Author) Other; Lengerke, C (Author) Other; David L (Author) FMUP; Rothen Rutishauser, B (Author) Other; Jacob, F (Author) Other; Heinzelmann Schwarz, V (Author) Other

Journal

Title: eLife

Vol. 9

Pages: 1-34

ISSN: 2050-084X

Publisher: eLife Sciences Publications

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00S-WVM

DOI: 10.7554/elife.59442

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 34