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.
authors: Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jia
authors: J
authors: Lu
authors: Xiangcang
authors: X
authors: Ye
authors: Fan
authors: F
authors: Fan
authors: Ling
authors: L
authors: Xia
authors: Rajat
authors: R
authors: Bhattacharya
authors: Seth
authors: S
authors: Bellister
authors: Federico
authors: F
authors: Tozzi
authors: Eric
authors: E
authors: Sceusi
authors: Yunfei
authors: Y
authors: Zhou
authors: Isamu
authors: I
authors: Tachibana
authors: Dipen M
authors: DM
authors: Maru
authors: David H
authors: DH
authors: Hawke
authors: Janusz
authors: J
authors: Rak
authors: Sendurai A
authors: SA
authors: Mani
authors: Patrick
authors: P
authors: Zweidler-McKay
authors: Lee M
authors: LM
authors: Ellis
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse
references: Biochem J. 2009 Oct 23;424(1):79-88
references: 19715556
references: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3219-24
references: 17296940
references: Int J Oncol. 2007 Jan;30(1):247-51
references: 17143535
references: Cancer Cell. 2007 Jan;11(1):69-82
references: 17222791
references: Science. 2009 Jun 26;324(5935):1670-3
references: 19556499
references: Clin Cancer Res. 2008 Nov 1;14(21):6751-60
references: 18980968
references: Nat Rev Cancer. 2010 Feb;10(2):138-46
references: 20094048
references: Cell Death Differ. 2002 Aug;9(8):842-55
references: 12107827
references: Nature. 2007 Jan 4;445(7123):106-10
references: 17122772
references: J Biol Chem. 2001 Aug 24;276(34):32022-30
references: 11427524
references: J Biol Chem. 2004 Apr 2;279(14):13285-8
references: 14769803
references: J Clin Oncol. 2008 Apr 20;26(12):2013-9
references: 18421054
references: N Engl J Med. 1991 Jan 3;324(1):1-8
references: 1701519
references: J Cell Biochem. 2004 Aug 15;92(6):1271-81
references: 15258909
references: Blood. 2011 Mar 10;117(10):2891-900
references: 21224467
references: Cancer Res. 2011 Sep 15;71(18):6061-72
references: 21788346
references: Cancer Cell. 2011 Jan 18;19(1):125-37
references: 21251616
references: Biochem J. 2010 Dec 1;432(2):283-94
references: 20819075
references: Development. 1997 Sep;124(17):3439-48
references: 9310338
references: Cancer Res. 1995 Sep 15;55(18):3964-8
references: 7664263
references: Cancer Res. 2010 Dec 1;70(23):9969-78
references: 21098716
references: Cell Stem Cell. 2010 Mar 5;6(3):251-64
references: 20207228
references: Curr Opin Oncol. 2007 Jan;19(1):61-4
references: 17133114
references: Nature. 2009 Jan 29;457(7229):608-11
references: 19092804
references: Nature. 2007 Jan 4;445(7123):111-5
references: 17122771
references: Nat Cell Biol. 2010 Nov;12(11):1046-56
references: 20972423
references: Nat Cell Biol. 2010 May;12(5):419-21
references: 20418873
references: Nat Cell Biol. 2010 May;12(5):468-76
references: 20418870
references: Cancer Res. 2009 Mar 1;69(5):1951-7
references: 19244128
references: Blood. 2008 Dec 15;112(13):4793-807
references: 19064739
references: Semin Oncol. 2011 Aug;38(4):552-60
references: 21810514
references: EMBO Rep. 2011 May;12(5):470-6
references: 21460795
references: Proc Natl Acad Sci U S A. 2011 May 10;108(19):7950-5
references: 21498687
references: Genetics. 1997 Feb;145(2):359-74
references: 9071590
references: Cancer Res. 2006 Feb 15;66(4):1883-90; discussion 1895-6
references: 16488983
references: Nature. 2006 Dec 21;444(7122):1032-7
references: 17183313
references: N Engl J Med. 1971 Nov 18;285(21):1182-6
references: 4938153
references: Oncology (Williston Park). 2008 Nov 30;22(13):1470-9
references: 19133603
references: Cancer Res. 2006 Oct 1;66(19):9339-44
references: 16990346
references: Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11842-9
references: 14504387
references: J Immunol. 2002 Oct 15;169(8):4273-8
references: 12370358
references: Immunity. 1998 Jan;8(1):43-55
references: 9462510
references: Cancer J. 2010 May-Jun;16(3):196-201
references: 20526096
references: Cancer Res. 2009 Apr 15;69(8):3382-9
references: 19336570
references: Nature. 1995 Sep 28;377(6547):355-8
references: 7566092