Abstract
Cell surface hypersialylation of human colorectal carcinoma (HCRC) cells correlates with increased metastatic potential after intrasplenic injection, while desialylation with various agents has been shown to inhibit hepatic metastases. In this study we examined the effects of desialylation of HCRC cell lines with a novel intracellular inhibitor of the CMP-sialic acid transport protein (KI-8110). HCRC cells, which are poorly differentiated and poorly metastatic in nude mice (Clone A and MIP-101) were compared to well-differentiated, highly metastatic cells (CX-1 and CCL-235). KI-8110 treatment has previously been shown to reduce sialic acid levels in each of these cell lines and to reduce hepatic metastases in CX-1 and CCL-235 cell lines. This study attempts to identify a mechanism by which desialylation inhibits hepatic metastases. After KI-8110 treatment,in vitro adhesion assays were performed with each cell line to examine binding to Kupffer cells and the extracellular matrix protein fibronectin. Binding of Clone A, CX-1, and CCL-235 to Kupffer cells was significantly increased after KI-8110 treatment. Desialylation had no significant effect on binding of HCRC cell lines to fibronectin. While the metastatic cascade involves many complex interactions, the cytotoxic effects of Kupffer cells in the hepatic sinusoid are known to be an important mechanism of host defense against tumor cells. Cell surface sialic acids may well mask Kupffer cell binding to HCRC cells, preventing their cytotoxic effects and enhancing the metastatic potential of circulating tumor cells.
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Boring CC, Squires TS and Tong T, 1991, Cancer statistics 1991.Cancer,41, 19–36.
Silverberg E and Lubera J, 1989, Cancer statistics.Cancer,37, 2–19.
Cady B, Stone MD, McDermott WV,et al. 1992, Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastasis.Arch Surg,127, 561–9.
Liotta L, 1992, Cancer cell invasion and metastasis.Sci Am, 54–63.
Hakomori S, 1985, Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives.Cancer Res,45, 2405–14.
Yogeeswaran G, 1983, Cell surface glycolipids and glycoproteins in malignant transformation.Adv Cancer Res,38, 289–350.
Yogeeswaran G and Salk PL, 1981, Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines.Science,212, 1514–16.
Sinha BK and Goldenberg GJ, 1974, The effect of trypsin and neuraminidase on the circulation and organ distribution of tumor cells.Cancer,34, 1956–61.
Bendetto A, Elia G, Sala A and Belardelli F, 1989, Hyposialylation of high-molecular-weight membrane glycoproteins parallels the loss of metastatic potential in wheat-germ agglutinin-resistant Friend leukemia cells.Int J Cancer,43, 126–33.
Fogel M, Altevogt P and Schirrmacher V, 1983, Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation.J Exp Med,157, 371–6.
Collard JG, Schijven JF,et al. 1986, Cell surface sialic acid and the invasive and metastatic potential of T-cell hybridomas.Cancer Res,46, 4080–6.
Yogeeswaran G and Salk PL, 1981, Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines.Science,212, 1514–16.
Miura S and Kim YS, 1986, Effect of tunicamycin on synthesis and secretion of carcinoembryonic antigen by human colonic adenocarcinoma cells.Int J Cancer,38, 197–205.
Irimura T, Gonzalez R and Nicolson GL, 1981, Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties.Cancer Res,41, 3411–18.
Humphries MJ, Matsumoto K, White SL and Olden K, 1980, Oligosaccharide modifications by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells.Proc Nat Acad Sci, USA,77, 399–403.
Harvey BE, Toth CA, Wagner HE, Steele GD Jr and Thomas P, 1992, Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.Cancer Res,52, 1775–9.
Harvey BE and Thomas P, 1993, Inhibition of CMP-sialic acid transport in human liver and colorectal cancer cell lines by sialic acid necleoside conjugate (KI-8110).Biochem Biophys Res Commun,190, 571–5.
Kijima-Suda I, Miyamoto Y, Toyoshima S, Itoh M and Osawa T, 1986, Inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid:nucleoside conjugate having sialyltransferase inhibiting activity.Cancer Res,46, 858–62.
Wagner HE, Thomas P,et al, 1990, Inhibition of sialic acid incorporation prevents hepatic metastases.Arch Surg,125, 351–4.
Phillips N, 1989, Kupffer cells and liver metastases.Cancer Metastasis Rev,8, 231–52.
Malter M, Federich E and Suss R, 1986, Liver as a tumor cell killing organ: Kupffer cells and natural killers.Cancer Res,46, 3055–60.
Cohen SA, Salazar D and Nolan JP, 1982, Natural cytotoxicity of isolated rat liver cells.J Immunol,129, 495–501.
Gardner CR, Wasserman AJ and Laskin DL, 1987, Differential sensitivity of tumor targets to liver macrophage-mediated cytotoxicity.Cancer Res,47, 6686–91.
Stanifold IH, Triger DR and Underwood JCE, 1983, Kupffer cell depletion in chronic liver disease: implications for hepatic carcinogenesis.Lancet,2, 431–3.
Pearson HJ,et al. 1986. The effect of Kupffer cell stimulation or depression on the development of liver metastases in the rat.Cancer Immunol Immunother,23, 214–16.
Decker T,et al. 1989, Comparative study of cytotoxicity, tumor necrosis factor and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages.J Leucocyte Biol,45, 139–46.
Gardner CR, Wasserman AJ and Laskin DL, 1991, Liver macrophage mediated cytotoxicity toward mastocytoma cells involves phagocytosis of tumor targets.Hepatology,14, 318–24.
Schlepper-Schafer J, Friedrich E and Kolb H, 1981, Galactosyl specific receptor on liver cells: binding site for tumor cells.Eur J Cell Biol,25, 95–102.
Niles R, Wilhelm S, Steele GD,et al. 1987, Isolation and characterization of an undifferentiated human colon carcinoma cell line (MIP-101).Cancer Invest,5, 545–52.
Wagner HE, Toth CA, Steele GD and Thomas P, 1992, Invasive and metastatic potential of human colorectal cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.Clin Exp Metastasis,10, 25–31.
Aminoff D, 1961, Methods for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialomucoids.Biochem J,81, 384–92.
Giavazzi R, Jessup JM, Campbell D, Walker S and Fidler I, 1986, Experimental nude mouse model of human colorectal cancer metastases.J Nat Cancer Inst,77, 1303–8.
Meterissian S, Steele Jr GD and Thomas P, 1993, Human and murine Kupffer cell function may be altered by both intrahepatic and intrasplenic tumor deposits.Clin Exp Metastasis,11, 175–82.
Toth CA, Thomas P, Broitman SA and Zamcheck N, 1985, Receptor mediated endocytosis of carcinoembryonic antigen by rat liver Kupffer cells.Cancer Res,45, 392–7.
Sinha BK and Goldenberg GJ, 1974, The effect of trypsin and neuraminidase on the circulation and organ distribution of tumor cells.Cancer,34, 1956–61.
Hagmar B and Norrby K, 1973, Influence of cultivation, trypsinization, and aggregation on the transplantability of melanoma B16 cells.Int J Cancer,11, 663–75.
Ruoslahti E, 1992, Control of cell motility and tumour invasion by extracellular matrix interactions.Brit J Cancer,66, 239–42.
Honn KV and Tang DG, 1992, Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix.Cancer Metastasis Rev,11, 353–75.
Schauer R, 1985, Sialic acids and their role as biological masks.TIBS, 357–360.
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Petrick, A.T., Meterissian, S., Steele, G. et al. Desialylation of metastatic human colorectal carcinoma cells facilitates binding to Kupffer cells. Clin Exp Metast 12, 108–116 (1994). https://doi.org/10.1007/BF01753977
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DOI: https://doi.org/10.1007/BF01753977