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Cancer Cell. 2013 Feb 11;23(2):171-85. doi: 10.1016/j.ccr.2012.12.021. Epub 2013 Jan 31.

Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1.

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1
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

We report a paracrine effect whereby endothelial cells (ECs) promote the cancer stem cell (CSC) phenotype of human colorectal cancer (CRC) cells. We showed that, without direct cell-cell contact, ECs secrete factors that promoted the CSC phenotype in CRC cells via Notch activation. In human CRC specimens, CD133 and Notch intracellular domain-positive CRC cells colocalized in perivascular regions. An EC-derived, soluble form of Jagged-1, via ADAM17 proteolytic activity, led to Notch activation in CRC cells in a paracrine manner; these effects were blocked by immunodepletion of Jagged-1 in EC-conditioned medium or blockade of ADAM17 activity. Collectively, ECs play an active role in promoting Notch signaling and the CSC phenotype by secreting soluble Jagged-1.

PMID:
23375636
PMCID:
PMC3574187
DOI:
10.1016/j.ccr.2012.12.021
[Indexed for MEDLINE]
Free PMC Article

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