Pericytes promote malignant ovarian cancer progression in mice and predict poor prognosis in serous ovarian cancer patients

Devbarna Sinha, Lynn Chong, Joshy George, Holger Schlüter, Susann Mönchgesang, Stuart Mills, Jason Li, Christopher Parish, David Bowtell, Pritinder Kaur*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)

    Abstract

    Purpose: The aim of this study was to investigate the role of pericytes in regulating malignant ovarian cancer progression. Experimental Design: The pericyte mRNA signature was used to interrogate ovarian cancer patient datasets to determine its prognostic value for recurrence and mortality. Xenograft models of ovarian cancer were used to determine if co-injection with pericytes affected tumor growth rate and metastasis, whereas coculture models were utilized to investigate the direct effect of pericytes on ovarian cancer cells. Pericyte markers were used to stain patient tissue samples to ascertain their use in prognosis. Results: Interrogation of two serous ovarian cancer patient datasets [the Australian Ovarian Cancer Study, n=215; and the NCI TCGA (The Cancer Genome Atlas), n=408] showed that a high pericyte score is highly predictive for poor patient prognosis. Co-injection of ovarian cancer (OVCAR-5 &-8) cells with pericytes in a xenograft model resulted in accelerated ovarian tumor growth, and aggressive metastases, without altering tumor vasculature. Pericyte co-culture in vitro promoted ovarian cancer cell proliferation and invasion. High aSMA protein levels in patient tissue microarrays were correlated with more aggressive disease and earlier recurrence. Conclusions: High pericyte score provides the best means to date of identifying patients with ovarian cancer at high risk of rapid relapse and mortality (mean progression-free survival time < 9 months). The stroma contains rare yet extremely potent locally resident mesenchymal stem cells-a subset of "cancer-associated fibroblasts" that promote aggressive tumor growth and metastatic dissemination, underlying the prognostic capacity of a high pericyte score to strongly predict earlier relapse and mortality.

    Original languageEnglish
    Pages (from-to)1813-1824
    Number of pages12
    JournalClinical Cancer Research
    Volume22
    Issue number7
    DOIs
    Publication statusPublished - 1 Apr 2016

    Fingerprint

    Dive into the research topics of 'Pericytes promote malignant ovarian cancer progression in mice and predict poor prognosis in serous ovarian cancer patients'. Together they form a unique fingerprint.

    Cite this