title: CD44s expression mitigates the phenotype of human colorectal cancer hepatic metastases.
abstract: Alterations in expression of the CD44 adhesion protein have been implicated in colorectal tumourigenesis. Overexpression of variant high molecular weight isoforms (especially CD44v6), as well as down-regulation of standard CD44 (CD44s), are postulated to result in increased tumourigenicity. We studied the metastatic phenotype produced by the expression of CD44s by stable transfection into a human colorectal carcinoma cell line, SW620, that shows absence of any CD44 expression. Splenic injection of 2 x 10(6) SW620 colon cancer cells into SCID mice was used to produce hepatic metastases. The animals were sacrificed at 6 weeks after injection and morphological end-points relating to macrometastases and micrometastases were studied CD44s expression was associated with decreased development of macroscopic tumours (0.9 vs 3.0 tumours/ mouse liver, p = 0.004), less extensive tumour replacement of the liver (2.6% vs 12.8%, p = 0. 04) and decreased numbers of micrometastases (3.8 x 10(-8) vs 7.9 x 10(-8) micrometastases/ microm2, p = 0.2). This study is the first to demonstrate the mitigating effect of CD44s expression on the hepatic metastatic phenotype in a colorectal carcinoma cell line that does not ordinarily express CD44.
authors.affiliation: Department of Surgery, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: P A
authors.initials: PA
authors.lastname: Pereira
authors.forename: U
authors.initials: U
authors.lastname: Rubenthiran
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: S
authors.initials: S
authors.lastname: Jothy
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D020033:Protein Isoforms; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018960:Hyaluronan Receptors; D020033:Protein Isoforms