Malignant and other properties of human colon carcinoma cells after suppression of sulfomucin production in vitro.
Although the loss of sulfomucins was known as an indicator of carcinogenesis and malignant progression of colonic epithelia, it was not known whether the loss was directly related to the malignant behavior of colon carcinoma cells. We have studied the biological properties of LS174T human colon carcinoma cells before and after suppression of sulfomucin production. Incorporation of [35S]-sulfate into high molecular weight mucins decreased after carcinoma cell treatment with 1.5% dimethylsulfoxide (DMSO) for 8 days. The amounts of sulfomucin determined using a sulfomucin-specific monoclonal antibody (mAb 91.9H), in Western blot and flowcytometric analyses, also decreased. In addition, the levels of MUC2 and MUC5B mucin gene expression measured by RT-PCR were reduced after DMSO-treatment, whereas the levels of MUC1, MUC5AC, and MUC6 mucin gene expression were not. The DMSO-treated cells were tested in vitro and in vivo for their properties. Differences were not detected in their anchorage-independent growth, anchorage-dependent growth, E-selectin-dependent cell adhesion or sensitivity to interleukin (IL)-2-activated lymphocyte cytolysis. When untreated or DMSO-treated LS174T cells were injected intrasplenically into nude mice, the treated cells lacking certain cell surface sulfomucins formed fewer metastatic colonies in the liver. These results suggest that the loss of sulfomucins by colonic epithelial cells during progression is not directly related to the enhanced malignant behavior.
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
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Tsuiji
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Nakatsugawa
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Ishigaki
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Irimura
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion; D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009077:Mucins / Q000096:biosynthesis* / Q000145:classification; D009368:Neoplasm Transplantation; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D009077:Mucins; D013431:Sulfates; C012564:sulfomucin; D004121:Dimethyl Sulfoxide