Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway

Vesselina G. Cooke, Valerie S. LeBleu, Doruk Keskin, Zainab Khan, Joyce T. O'Connell, Yingqi Teng, Michael B. Duncan, Liang Xie, Genta Maeda, Sylvia Vong, Hikaru Sugimoto, Rafael M. Rocha, Aline Damascena, Ricardo R. Brentani, Raghu Kalluri

Research output: Contribution to journalArticlepeer-review

324 Scopus citations

Abstract

The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depletion suppressed tumor growth but enhanced metastasis. Pericyte depletion was further associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation. Silencing of Twist or use of a Met inhibitor suppressed hypoxia and EMT/Met-driven metastasis. In addition, poor pericyte coverage coupled with high Met expression in cancer cells speculates the worst prognosis for patients with invasive breast cancer. Collectively, our study suggests that pericytes within the primary tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis.

Original languageEnglish (US)
Pages (from-to)66-81
Number of pages16
JournalCancer Cell
Volume21
Issue number1
DOIs
StatePublished - Jan 17 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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