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

219 Citations (Scopus)

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

Fingerprint

Neoplastic Stem Cells
Colorectal Neoplasms
Endothelial Cells
Phenotype
Conditioned Culture Medium
Jagged-1 Protein

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1. / Lu, Jia; Ye, Xiangcang; Fan, Fan; Xia, Ling; Bhattacharya, Rajat; Bellister, Seth; Tozzi, Federico; Sceusi, Eric; Zhou, Yunfei; Tachibana, Isamu; Maru, Dipen M.; Hawke, David H.; Rak, Janusz; Mani, Sendurai A.; Zweidler-McKay, Patrick; Ellis, Lee M.

In: Cancer Cell, Vol. 23, No. 2, 11.02.2013, p. 171-185.

Research output: Contribution to journalArticle

Lu, J, Ye, X, Fan, F, Xia, L, Bhattacharya, R, Bellister, S, Tozzi, F, Sceusi, E, Zhou, Y, Tachibana, I, Maru, DM, Hawke, DH, Rak, J, Mani, SA, Zweidler-McKay, P & Ellis, LM 2013, 'Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1', Cancer Cell, vol. 23, no. 2, pp. 171-185. https://doi.org/10.1016/j.ccr.2012.12.021
Lu, Jia ; Ye, Xiangcang ; Fan, Fan ; Xia, Ling ; Bhattacharya, Rajat ; Bellister, Seth ; Tozzi, Federico ; Sceusi, Eric ; Zhou, Yunfei ; Tachibana, Isamu ; Maru, Dipen M. ; Hawke, David H. ; Rak, Janusz ; Mani, Sendurai A. ; Zweidler-McKay, Patrick ; Ellis, Lee M. / Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1. In: Cancer Cell. 2013 ; Vol. 23, No. 2. pp. 171-185.
@article{49730e9e6a6846bd93a1dfb4907d7644,
title = "Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1",
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.",
author = "Jia Lu and Xiangcang Ye and Fan Fan and Ling Xia and Rajat Bhattacharya and Seth Bellister and Federico Tozzi and Eric Sceusi and Yunfei Zhou and Isamu Tachibana and Maru, {Dipen M.} and Hawke, {David H.} and Janusz Rak and Mani, {Sendurai A.} and Patrick Zweidler-McKay and Ellis, {Lee M.}",
year = "2013",
month = "2",
day = "11",
doi = "10.1016/j.ccr.2012.12.021",
language = "English (US)",
volume = "23",
pages = "171--185",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1

AU - Lu, Jia

AU - Ye, Xiangcang

AU - Fan, Fan

AU - Xia, Ling

AU - Bhattacharya, Rajat

AU - Bellister, Seth

AU - Tozzi, Federico

AU - Sceusi, Eric

AU - Zhou, Yunfei

AU - Tachibana, Isamu

AU - Maru, Dipen M.

AU - Hawke, David H.

AU - Rak, Janusz

AU - Mani, Sendurai A.

AU - Zweidler-McKay, Patrick

AU - Ellis, Lee M.

PY - 2013/2/11

Y1 - 2013/2/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84873728505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873728505&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2012.12.021

DO - 10.1016/j.ccr.2012.12.021

M3 - Article

C2 - 23375636

AN - SCOPUS:84873728505

VL - 23

SP - 171

EP - 185

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -