title: Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface.
abstract: Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the "protective shield" of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galbeta1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis.
authors.affiliation: Gastroenterology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xiuli
authors.initials: X
authors.lastname: Guo
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.forename: Philip C
authors.initials: PC
authors.lastname: Stone
authors.forename: John
authors.initials: J
authors.lastname: Hilkens
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rhodes
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002462:Cell Membrane; D016764:Cell Polarity; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding
chemical_list: D019040:E-Selectin; D037502:Galectin 3; D018960:Hyaluronan Receptors; C060192:MUC1 protein, human; D018396:Mucin-1
references.citation: J Clin Invest. 1991 Mar;87(3):1037-45
references.pmid: 1999484
references.citation: Clin Cancer Res. 2000 Apr;6(4):1389-93
references.pmid: 10778968
references.citation: Am J Pathol. 2008 Dec;173(6):1839-52
references.pmid: 18988806
references.citation: Glycoconj J. 2004;19(7-9):543-9
references.pmid: 14758078
references.citation: Clin Exp Metastasis. 2005;22(6):475-83
references.pmid: 16320110
references.citation: Int J Cancer. 2001 Dec 15;94(6):783-91
references.pmid: 11745478
references.citation: Cancer Cell. 2005 Feb;7(2):167-78
references.pmid: 15710329
references.citation: Glycoconj J. 1996 Oct;13(5):693-707
references.pmid: 8909996
references.citation: Cancer Metastasis Rev. 2001;20(3-4):245-77
references.pmid: 12085965
references.citation: Cancer. 2000 Apr 1;88(7):1536-43
references.pmid: 10738210
references.citation: Oral Oncol. 2008 Jan;44(1):86-93
references.pmid: 17350328
references.citation: Trends Cell Biol. 2006 Sep;16(9):467-76
references.pmid: 16904320
references.citation: Gastroenterology. 1994 Feb;106(2):353-61
references.pmid: 7905449
references.citation: J Biol Chem. 2007 Jan 5;282(1):773-81
references.pmid: 17090543
references.citation: Histol Histopathol. 1999 Oct;14(4):1153-8
references.pmid: 10506931
references.citation: Neoplasia. 2006 Nov;8(11):939-48
references.pmid: 17132226
references.citation: J Cell Biol. 1995 Apr;129(1):255-65
references.pmid: 7698991
references.citation: J Biol Chem. 1996 Dec 27;271(52):33325-34
references.pmid: 8969192
references.citation: Glycobiology. 2001 Jul;11(7):587-92
references.pmid: 11447138
references.citation: Gastroenterology. 1998 Aug;115(2):287-96
references.pmid: 9679034
references.citation: Glycoconj J. 1997 Aug;14(5):569-76
references.pmid: 9298689
references.citation: J Biol Chem. 2003 Feb 7;278(6):4127-34
references.pmid: 12438311
references.citation: Cancer Res. 2001 Jun 15;61(12):4851-7
references.pmid: 11406562
references.citation: Cancer Metastasis Rev. 2008 Mar;27(1):75-83
references.pmid: 18046511
references.citation: Clin Exp Metastasis. 2008;25(4):305-24
references.pmid: 17906932
references.citation: Nat Med. 2008 May;14(5):518-27
references.pmid: 18438415
references.citation: Curr Opin Cell Biol. 2003 Oct;15(5):531-8
references.pmid: 14519387
references.citation: Oncology. 2001;61(2):147-55
references.pmid: 11528254
references.citation: Cancer. 1998 Mar 15;82(6):1019-27
references.pmid: 9506345
references.citation: Int J Oncol. 2005 Nov;27(5):1289-97
references.pmid: 16211224
references.citation: Biochemistry. 2002 Aug 6;41(31):9946-61
references.pmid: 12146959
references.citation: Biol Cell. 2004 Mar;96(2):145-51
references.pmid: 15050369
references.citation: Tumour Biol. 1998;19 Suppl 1:35-45
references.pmid: 9422087
references.citation: Trends Biochem Sci. 1992 Sep;17(9):359-63
references.pmid: 1412714
references.citation: J Biol Chem. 1990 Apr 5;265(10):5573-8
references.pmid: 2318825
references.citation: Blood. 2003 Oct 15;102(8):2828-34
references.pmid: 12829609
references.citation: Clin Cancer Res. 2001 Mar;7(3):661-8
references.pmid: 11297262
references.citation: J Cell Biochem. 1996 Mar 15;60(4):538-49
references.pmid: 8707893
references.citation: Acta Oncol. 2007;46(3):316-23
references.pmid: 17450466
references.citation: J Biol Chem. 2004 Jul 9;279(28):29386-90
references.pmid: 15169768
references.citation: Cancer Res. 2004 Aug 15;64(16):5702-11
references.pmid: 15313910
references.citation: Breast Cancer. 2006;13(1):58-63
references.pmid: 16518063
references.citation: Clin Exp Metastasis. 1999 May;17(3):183-92
references.pmid: 10432003
references.citation: Nat Rev Cancer. 2005 Jan;5(1):29-41
references.pmid: 15630413
references.citation: Mol Biol Cell. 1996 Apr;7(4):565-77
references.pmid: 8730100
references.citation: Clin Exp Dermatol. 2006 Jan;31(1):105-9
references.pmid: 16309497
references.citation: Glycoconj J. 2007 Nov;24(8):411-20
references.pmid: 17457671
references.citation: Cancer Res. 1999 Sep 1;59(17):4427-34
references.pmid: 10485493