Geburtshilfe Frauenheilkd 2020; 80(10): e193
DOI: 10.1055/s-0040-1718145
Poster
Mittwoch, 7.10.2020
Gynäkologische Onkologie II

Integrin α2-collagen interaction promotes ovarian cancer metastasis

Y.-L Huang
1   Universitätsspital Basel, Department of Biomedicine, Basel, Schweiz
,
C.-Y Liang
1   Universitätsspital Basel, Department of Biomedicine, Basel, Schweiz
,
D Ritz
2   Universität Basel, Biozentrum, Basel, Schweiz
,
R Coelho
3   University of Porto, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
,
D Septiadi
4   University of Fribourg, Adolphe Merkle Institute, Fribourg, Schweiz
,
M Estermann
4   University of Fribourg, Adolphe Merkle Institute, Fribourg, Schweiz
,
N Rimmer
1   Universitätsspital Basel, Department of Biomedicine, Basel, Schweiz
,
T Vlajnic
5   Universitätsspital Basel, Institute of Pathology, Basel, Schweiz
,
L David
3   University of Porto, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
,
B Rothen-Rutishauser
4   University of Fribourg, Adolphe Merkle Institute, Fribourg, Schweiz
,
F Jacob
1   Universitätsspital Basel, Department of Biomedicine, Basel, Schweiz
,
V Heinzelmann-Schwarz
1   Universitätsspital Basel, Department of Biomedicine, Basel, Schweiz
6   Universitätsspital Basel, Gynecological Cancer Center, Basel, Schweiz
› Author Affiliations
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    Objective The contribution of the extracellular matrix (ECM) in the pre-metastatic niche for early steps of cancer cell metastasis remain largely unexplored. Therefore,we aim to study the interplay between integrin-ECM in mediating ovarian cancer cell metastasis.

    Methods CRISPR-Cas9, ECM adhesion assay, mesothelial clearance, in vivo xenograft, tissue microarray, proteomics.

    Results We describe a unique expression of collagens in normal omentum, representing the most important metastatic site in advanced epithelial ovarian cancer. Elevated levels of various collagens in omental metastatic disease coincides with poor outcome in large transcriptomic datasets. We also identified that collagen-binding receptor, integrin alpha 2 (ITGA2) is highly abundant in matched patient-derived tissues and ascites. ITGA2-collagen mediated cancer cell adhesion is reversible using gene-edited strategy. Moreover, ITGA2 drives directed cell migration, anoikis resistance and mesothelial clearance in vitro and promotes metastasis in vivo. The patient-derived ex vivo cultures can be pharmacologically inhibited. Mechanistically, loss of ITGA2-dependent signaling downregulates the focal adhesion kinase signaling. Specific inhibition of ITGA2-mediated cancer cell-collagen adhesion by TC-I-15 or Defactinib may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.

    Zoom Image
    Abb.1 ITGA2-collagen interaction drives ovarian cancer metastasis.

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    Publication History

    Article published online:
    07 October 2020

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    Zoom Image
    Abb.1 ITGA2-collagen interaction drives ovarian cancer metastasis.