Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Danilo Ritz
Proteomics core facility, Biozentrum, University of Basel, Basel, Switzerland
Ricardo Coelho
Differentiation and Cancer group, Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
Dedy Septiadi
Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
Manuela Estermann
Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
Cécile Cumin
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Natalie Rimmer
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Andreas Schötzau
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Mónica Núñez López
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
André Fedier
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Stem Cells and Hematopoiesis, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
Tatjana Vlajnic
Institute of Pathology, University Hospital Basel, Basel, Switzerland
Diego Calabrese
Histology Core Facility, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Claudia Lengerke
Stem Cells and Hematopoiesis, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Internal Medicine, Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
Leonor David
Differentiation and Cancer group, Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
Barbara Rothen-Rutishauser
Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
Viola Heinzelmann-Schwarz
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland; Gynecological Cancer Center, University Hospital Basel, Basel, Switzerland
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.
