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Human colon carcinoma cells with increased invasive capacity obtained by selection for sialyl-dimeric Lex antigen

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Abstract

Sialyl-dimeric Lex antigen (NeuAcα2-3Galβ1-4[Fuc-α1-3]GlcNAcβ1-3Galβ1-4[Fucα1-3]GlcNAcβ1-R; SLX) is an oncodevelopmental carbohydrate antigen expressed both on glycolipids and on mucin-like glycoproteins in human colorectal carcinomas. The levels are higher in primary tumors at advanced stages than in tumors at early stages, and metastatic lesions contain a greater quantity of this antigen than corresponding primary tumors. To study whether this antigen influences the metastatic behavior of tumor cells, we selected SLX variant cells from the human colon carcinoma cell line KM12C using the specific monoclonal antibody FH6. We obtained two stable cell lines: a high expresser (KM12-HX) and a low expresser (KM12-LX) of this antigen. The growth rate of these cells are similar. A mucin-like glycoprotein reactive with monoclonal antibody FH6 was detected after electrophoretic separation of KM12-HX cell lysates but not of KM12-LX lysates. The degree of invasion was compared in assays in vitro using matrigel-coated filter membranes. The number of KM12-HX cells that invaded the membranes was significantly higher than KM12-LX cells.

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    This work was supported by NIH Grants RO1-CA39319 and RO1-CA50231, by Texas Higher Education Program Grant 1549 to Tatsuro Irimura, and in part by grants from the NIH (R35-CA44352) to Garth L. Nicolson.

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