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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Feb 5

PMID 23375636

Citations 255

Authors

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

Affiliations

Soon will be listed here.

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.

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