title: Expression of carbohydrate-antigen sialyl-Lewis a on colon cancer cells promotes xenograft growth and angiogenesis in nude mice.
abstract: We investigated the role of carbohydrate antigen sialyl-Lewis a (sLea), an E-selectin ligand and epitope of tumor marker CA19.9, in the development of xenografts in nude mice. To this end, animals were inoculated with the human colon cancer cell line HCT-15, expressing no Lewis antigens, or with a clone expressing sLea (HCT-15-T5). The size of HCT-15-T5 xenografts appeared larger than those of HCT-15 and their average weight was over twice bigger. In both xenografts the mitotic index was found elevated, as determined by Ki-67 assay, and no apoptosis was detected in the tumor cells by both caspase 8 or TUNEL assays. Some apoptotic signals were instead detected in the vessels. Conversely, microvessel density, determined through CD-31 immunohistochemistry, was found 3.2-folds bigger in HCT-15-T5 xenografts (p<0.012). Only the membranes of HCT-15-T5 cells grown as xenografts reacted intensively with the anti CA19.9 antibody 1116-NS-19-9 by immunofluorescence, but not by immunohistochemistry. Unknown structures were instead stained by such technique in both xenografts, as were in mouse tissues not expressing the antigen and in human colon adenocarcinoma. We conclude that expression of sLea on the surface of colon cancer cells improves xenograft growth and is associated with enhanced angiogenesis, while immunohistochemistry with 1116-NS-19-9 antibody appears not suitable to determine CA19.9 expression.
authors.affiliation: Department of Health Sciences, San Paolo Hospital, University of Milan, 20142 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Terraneo
authors.forename: Laura
authors.initials: L
authors.lastname: Avagliano
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.forename: Paola
authors.initials: P
authors.lastname: Bianciardi
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.forename: Gaetano Pietro
authors.initials: GP
authors.lastname: Bulfamante
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
authors.forename: Marco
authors.initials: M
authors.lastname: Trinchera
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018395:CA-19-9 Antigen / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D019040:E-Selectin
keywords: Carbohydrate antigen; Colon cancer; E-selectin; H&E; TUNEL; Tumor angiogenesis; Tumor marker; hematoxylin⬜eosin; sLea; sLex; sialyl-Lewis a, NeuAca2-3Galø1-3[Fuca1-4]GlcNAc; sialyl-Lewis x, NeuAca2-3Galø1-4[Fuca1-3]GlcNAc; terminal deoxynucleotidyl transferase dUTP nick end labeling