Endoglin regulates cancer-stromal cell interactions in prostate tumors

Diana Romero, Christine O'Neill, Aleksandra Terzic, Liangru Contois, Kira Young, Barbara A. Conley, Raymond C. Bergan, Peter C. Brooks, Calvin P.H. Vary

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Endoglin is an accessory receptor for TGF-β that has been implicated in prostate cancer cell detachment, migration, and invasiveness. However, the pathophysiologic significance of endoglin with respect to prostate tumorigenesis has yet to be fully established. In this study, we addressed this question by investigation of endoglin-dependent prostate cancer progression in a TRAMP (transgenic adenocarcinoma mouse prostate) mouse model where endoglin was genetically deleted. In this model, endoglin was haploinsufficient such that its allelic deletion slightly increased the frequency of tumorigenesis, yet produced smaller, less vascularized, and less metastatic tumors than TRAMP control tumors. Most strikingly, TRAMP:eng+/--derived tumors lacked the pronounced infiltration of carcinoma-associated fibroblasts (CAF) that characterize TRAMP prostate tumors. Studies in human primary prostate-derived stromal cells (PrSC) confirmed that suppressing endoglin expression decreased cell proliferation, the ability to recruit endothelial cells, and the ability to migrate in response to tumor cell-conditioned medium. We found increased levels of secreted insulin-like growth factor-binding proteins (IGFBP) in the conditioned medium from endoglin-deficient PrSCs and that endoglin-dependent regulation of IGFBP-4 secretion was crucial for stromal cell-conditioned media to stimulate prostate tumor cell growth. Together, our results firmly establish the pathophysiologic involvement of endoglin in prostate cancer progression; furthermore, they show how endoglin acts to support the viability of tumor-infiltrating CAFs in the tumor microenvironment to promote neovascularization and growth.

Original languageEnglish (US)
Pages (from-to)3482-3493
Number of pages12
JournalCancer Research
Volume71
Issue number10
DOIs
StatePublished - May 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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