CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in ovarian cancer patients

Oncogenesis
C WindmüllerH Bronger

Abstract

Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian cancer (EOC), but the underlying mechanisms have not been fully elucidated. The CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites, but its role in ovarian cancer metastasis is largely unknown. Herein, we first screened two independent cohorts of high-grade serous ovarian cancers (HGSCs, discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3 expression. In primary tumors, CXCR3 was particularly overexpressed by tumor cells at the invasive front. In intraabdominal metastases, tumor cells revealed a strong CXCR3 expression regardless of its expression in the corresponding primary tumor, suggesting a selection of CXCR3-overexpressing cancer cells into peritoneal niches. In support of this, CXCR3 mediated the migration of tumor cell lines OVCAR3 and SKOV3 toward malignant ascites, which was inhibited by a monoclonal anti-CXCR3 antibody in vitro. These results were prospectively validated in ascites-derived tumor cells from EOC patients ex vivo (n=9). Moreover, tumor cell-associated overexpression of CXCR3 in advanced ovarian cancer patients was associated with a reduced progression-free survival (PFS) and...Continue Reading

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Citations

Sep 5, 2019·Cancer Metastasis Reviews·Holger BrongerTobias Dreyer
Aug 19, 2017·Stem Cells International·Manuel Varas-GodoySebastián E Illanes
Oct 16, 2018·Frontiers in Immunology·Katharina Helene SusekAndreas Lundqvist
Jul 3, 2021·Diagnostics·Sung-Woog KangAndrew N Stephens

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
flow cytometry
ELISA

Software Mentioned

Flowing
SPSS

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