Journal article
Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium
Cancer research (Chicago, Ill.), Vol.71(3), pp.976-987
02/01/2011
DOI: 10.1158/0008-5472.CAN-10-3396
PMCID: PMC3032824
PMID: 21148069
Abstract
It is well known that tumor-derived pro-angiogenic 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 under investigated. 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 datasets 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.
Details
- Title: Subtitle
- Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium
- Creators
- Dana M. Brantley-Sieders - Vanderbilt UniversityCharlene M. Dunaway - Vanderbilt UniversityMeghana Rao - Vanderbilt UniversitySarah Short - Vanderbilt UniversityYoonha Hwang - Vanderbilt UniversityYandong Gao - Vanderbilt University School of MedicineDeyu Li - Vanderbilt UniversityAixiang Jiang - Vanderbilt UniversityYu Shyr - Vanderbilt UniversityJane Y. Wu - Vanderbilt University School of MedicineJin Chen - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.71(3), pp.976-987
- DOI
- 10.1158/0008-5472.CAN-10-3396
- PMID
- 21148069
- PMCID
- PMC3032824
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 02/01/2011
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984420839102771
Metrics
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