Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of slit2 tumor suppressor function in endothelium

Dana M. Brantley-Sieders, Charlene M. Dunaway, Meghana Rao, Sarah Short, Yoonha Hwang, Yandong Gao, Deyu Li, Aixiang Jiang, Yu Shyr, Jane Y. Wu, Jin Chen

研究成果: Article同行評審

45 引文 斯高帕斯(Scopus)

摘要

It is well known that tumor-derived proangiogenic factors induce neovascularization to facilitate tumor growth and malignant progression. However, the concept of "angiocrine" signaling, in which signals produced by endothelial cells elicit tumor cell responses distinct from vessel function, has been proposed, yet remains underinvestigated. Here, we report that angiocrine factors secreted from endothelium regulate tumor growth and motility. We found that Slit2, which is negatively regulated by endothelial EphA2 receptor, is one such tumor suppressive angiocrine factor. Slit2 activity is elevated in EphA2-deficient endothelium. Blocking Slit activity restored angiocrine-induced tumor growth/motility, whereas elevated Slit2 impaired growth/motility. To translate our findings to human cancer, we analyzed EphA2 and Slit2 expression in human cancer. EphA2 expression inversely correlated with Slit2 in the vasculature of invasive human ductal carcinoma samples. Moreover, analysis of large breast tumor data sets revealed that Slit2 correlated positively with overall and recurrence-free survival, providing clinical validation for the tumor suppressor function for Slit2 in human breast cancer. Together, these data support a novel, clinically relevant mechanism through which EphA2 represses Slit2 expression in endothelium to facilitate angiocrine-mediated tumor growth and motility by blocking a tumor suppressive signal.

原文English
頁(從 - 到)976-987
頁數12
期刊Cancer Research
71
發行號3
DOIs
出版狀態Published - 2011 二月 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

指紋 深入研究「Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of slit2 tumor suppressor function in endothelium」主題。共同形成了獨特的指紋。

引用此