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 language | English (US) |
|---|---|
| Pages (from-to) | 171-185 |
| Number of pages | 15 |
| Journal | Cancer Cell |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 11 2013 |
| Externally published | Yes |
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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 journal › Article
}
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.
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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 -