Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1

Jia Lu, Xiangcang Ye, Fan Fan, Ling Xia, Rajat Bhattacharya, Seth Bellister, Federico Tozzi, Eric Sceusi, Yunfei Zhou, Isamu Tachibana, Dipen M. Maru, David H. Hawke, Janusz Rak, Sendurai A. Mani, Patrick Zweidler-McKay, Lee M. Ellis

Research output: Contribution to journalArticle

240 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)171-185
Number of pages15
JournalCancer Cell
Volume23
Issue number2
DOIs
StatePublished - Feb 11 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Lu, J., Ye, X., Fan, F., Xia, L., Bhattacharya, R., Bellister, S., Tozzi, F., Sceusi, E., Zhou, Y., Tachibana, I., Maru, D. M., Hawke, D. H., Rak, J., Mani, S. A., Zweidler-McKay, P., & Ellis, L. M. (2013). Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1. Cancer Cell, 23(2), 171-185. https://doi.org/10.1016/j.ccr.2012.12.021