title: Pericytes Promote Malignant Ovarian Cancer Progression in Mice and Predict Poor Prognosis in Serous Ovarian Cancer Patients.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of pericytes in regulating malignant ovarian cancer progression.
  
  
  METHODS
  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 co-culture 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 αSMA 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.
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Bioinformatics Core Facility, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Devbarna
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Lynn
authors.initials: L
authors.lastname: Chong
authors.affiliation: Cancer Genetics & Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Joshy
authors.initials: J
authors.lastname: George
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Holger
authors.initials: H
authors.lastname: Schlüter
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Susann
authors.initials: S
authors.lastname: Mönchgesang
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Mills
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.affiliation: The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parish
authors.affiliation: Cancer Genetics & Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. Department of Pathology, University of Melbourne, Parkville, Victoria, Australia. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Bowtell
authors.affiliation: Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia. pritinder.kaur@hudson.org.au.
authors.forename: Pritinder
authors.initials: P
authors.lastname: Kaur
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D020286:Pericytes / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence; D023041:Xenograft Model Antitumor Assays
chemical_list: D000199:Actins