@article{f234c826ff1b414db60cd584fd818bf7,
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.\}",
note = "Funding Information: This work was supported in part by National Institutes of Health (NIH) Cancer Center support grant CA016672, NIH grant T32CA009599 (to S.B., F.T., and E.S.), NIH grant R01CA157880 (to L.M.E.), Department of Defense grant CA100879 (to L.M.E.), the William C. Liedtke, Jr., Chair in Cancer Research (to L.M.E.), and an R.E. “Bob” Smith Fellowship (to S.S.). The authors thank Li Huang and Menashe Bar-Eli, from the Department of Cancer Biology, M.D. Anderson Cancer Center (MDACC), for molecular subcloning of full-length Jagged-1 and ADAM17. The authors thank John Ladbury, from The Center of Biomolecular Structure and Function, for assistance in identification of the Jagged-1 cleavage site. The authors thank Francesco Stingo, from Department of Biostatistics, for statistical support. The authors thank Zach Bohannan, Sunita Patterson, and Claire Dawn from the Department of Scientific Publications, and Rita Hernandez from the Departments of Surgical Oncology and Cancer Biology for editorial assistance. All of the above are from the MDACC. L.M.E. serves as an ad hoc consultant for Genentech/Roche. ",
year = "2013",
month = feb,
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",
}