PUBLICATION
Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis
- Authors
- Huang, Y.L., Liang, C.Y., Ritz, D., Coelho, R., Septiadi, D., Estermann, M., Cumin, C., Rimmer, N., Schötzau, A., Núñez López, M., Fedier, A., Konantz, M., Vlajnic, T., Calabrese, D., Lengerke, C., David, L., Rothen-Rutishauser, B., Jacob, F., Heinzelmann-Schwarz, V.
- ID
- ZDB-PUB-201008-12
- Date
- 2020
- Source
- eLIFE 9: (Journal)
- Registered Authors
- Konantz, Martina, Lengerke, Claudia
- Keywords
- Cell adhesion, Collagen, Peritoneal metastasis, cancer biology, cell biology, focal adhesion kinase, human, integrin alpah 2, mouse, omentum, zebrafish
- MeSH Terms
-
- Animals
- Carcinoma, Ovarian Epithelial/metabolism
- Cell Line, Tumor
- Collagen/metabolism*
- Female
- Integrin alpha2/metabolism*
- Mice
- Neoplasm Metastasis/physiopathology*
- Omentum/physiopathology*
- Peritoneum/physiopathology*
- Zebrafish
- PubMed
- 33026975 Full text @ Elife
Citation
Huang, Y.L., Liang, C.Y., Ritz, D., Coelho, R., Septiadi, D., Estermann, M., Cumin, C., Rimmer, N., Schötzau, A., Núñez López, M., Fedier, A., Konantz, M., Vlajnic, T., Calabrese, D., Lengerke, C., David, L., Rothen-Rutishauser, B., Jacob, F., Heinzelmann-Schwarz, V. (2020) Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis. eLIFE. 9:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping