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

被引：431

作者：

Lu, Jia ^{[1
]}

Ye, Xiangcang ^{[1
]}

Fan, Fan ^{[1
]}

Xia, Ling ^{[1
]}

Bhattacharya, Rajat ^{[1
]}

Bellister, Seth ^{[2
]}

Tozzi, Federico ^{[2
]}

Sceusi, Eric ^{[2
]}

Zhou, Yunfei ^{[1
]}

Tachibana, Isamu ^{[1
]}

Maru, Dipen M. ^{[3
]}

Hawke, David H. ^{[3
]}

Rak, Janusz ^{[6
]}

Mani, Sendurai A. ^{[4
]}

Zweidler-McKay, Patrick ^{[5
]}

Ellis, Lee M. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA

[6] McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3Z 2Z3, Canada

来源：

CANCER CELL | 2013年 / 23卷 / 02期

基金：

美国国家卫生研究院;

关键词：

SELF-RENEWAL; GROWTH-FACTOR; COLON-CANCER; TUMOR ANGIOGENESIS; ANGIOCRINE FACTORS; NOTCH; DIFFERENTIATION; METASTASIS; RECEPTOR; NICHE;

D O I：

10.1016/j.ccr.2012.12.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：171 / 185

页数：15

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