Abstract
Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.
Similar content being viewed by others
References
Poste G and Fidler IJ, 1980, The pathogenesis of cancer metastasis. Nature, 283283, 139–46.
Vlodavsky I and Gospodarowicz D, 1981, Respective roles of laminin and fibronectin in adhesion of human carcinoma and sarcoma cells. Nature, 289, 304–6.
Terranova VP, Liotta LA, Russo RG and Martin GR, 1982, Role of laminin in the attachment and metastasis of murine tumor cells. Cancer Res, 42, 2265–9.
Terranova VP, Williams JE, Liotta LA and Martin GR, 1984, Modulation of the metastatic activity of melanoma cells by laminin and fibronectin. Science, 226, 982–5.
Humphries MJ, Olden K and Yamada KM, 1986, A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science, 233, 467–79.
6. Humphries MJ, Yamada KM and Olden K, 1988, Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells. J Clin Invest, 81, 782–90.
Saiki I, Iida J, Murata J, et al. 1989, Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules. Cancer Res, 49, 3815–22.
Kumagai H, T ajima M, Ueno Y, Giga-Hama Y and Ohba M, 1991, Effect of cyclic RGD peptide on cell adhesion and tumor metastasis. Biochem Biophys Res Commun, 177, 74–82.
Soszka T, Knudsen KA, Beviglia L, Rossi C, Poggi A and Niewiarowski S, 1991, Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, and RGD-containing peptide isolated from the venom of Trimeresurus albolabris. Exp Cell Res, 196, 6–12.
Iwamoto Y, Robey FA, Graf J, et al. 1987, YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science, 238, 1132–4.
Nomizu M, Yamamura K, Kleinman HK and Yamada Y, 1993, Multimeric forms of Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide enhance the inhibition of tumor growth and metastasis. Cancer Res, 53, 3459–61.
Tuszynski GP, Rothman VL, Deutch AH, Hamilton BK and Eyal J, 1992, Biological activities of peptides and peptide analogues derived from common sequences present in thrombospondin, properdin, and malarial proteins. J Cell Biol, 116, 209–17.
Fujita S, Suzuki H, Kinoshita M and Hirohashi S, 1992, Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin β1 subunit antibody. Jap J Cancer Res, 83, 1317–26.
Yamagata M, Suzuki S, Akiyama SK, Yamada KM and Kimata K, 1989, Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates. J Biol Chem, 264, 8012–18.
Sugiura N, Sakurai K, Hori Y, Karasawa K, Suzuki S and Kimata K, 1993, Preparation of lipid-derivatized glycosaminoglycans to probe a regulatory function of the carbohydrate moieties of proteoglycans in cell-matrix interaction. J Biol Chem, 268, 15779–87.
Yamagata M, Saga S, Kato M, Bernfield M and Kimata K, 1993, Selective distributions of proteoglycans and their ligands in pericellular matrix of cultured fibroblasts: Implications for their roles in cell-substratum adhesion. J Cell Sci, 106, 55–65.
Yamagata M and Kimata K, 1994, Repression of a malignant cell-substratum adhesion phenotype by inhibiting the production of the anti-adhesive proteoglycan, PG-M/versican. J Cell Sci, 107, 2581–90.
Murata J, Saiki I, Nishimura S, Nishi N, Tokura S and Azuma I, 1989, Inhibitory effect of chitin heparinoids on the lung metastasis of B16-BL6 melanoma. Jap J Cancer Res, 80, 866–72.
Saiki I, Murata J, Nakajima M, Tokura S and Azuma I, 1990, Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells. Cancer Res, 50, 3631–37.
Kimata K, Oike Y, Tani K, et al. 1986, A large chondroitin sulfate proteoglycan (PG-M) synthesized before chondrogenesis in the limb bud of chick embryo. J Biol Chem, 261, 13517–25.
Yamagata M, Yamada KM, Yoneda M, Suzuki S and Kimata K, 1986, Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin. J Biol Chem, 261, 13526–35.
Shinomura T, Nishida Y, Ito K and Kimata K, 1994, cDNA cloning of PG-M, a large chondroitin sulfate proteoglycan expressed during chondrogenesis in chick limb buds. J Biol Chem, 269, 27603–9.
Oike Y, Kimata K, Shinomura T, Nakazawa K and Suzuki S, 1980, Structural analysis of chick-embryo cartilage proteoglycan by selective degradation with chondroitin lyases (chondroitinases) and end-b-Dgalactosidase (keratanase). Biochem J, 191, 193–207.
Ogamo AK, Matsuzaki K, Uchiyama H and Nagasawa K, 1982, Preparation and properties of fluorescent glycosaminoglycuronans labeled with 5-aminofluorescein. Carbohydrate Res, 105, 69–85.
Fidler IJ, 1973, Selection of successive tumour lines for metastasis. Nature, 242, 148–9.
Ruoslahti E, Hayman EG, Pierschbacher M and Engvall E, 1982, Fibronectin: purification, immunochemical properties, and biological activities. Meth Enzymol, 82, 803–31.
Albini A, Iwamoto Y, Kleinman HK, et al. 1987, A rapid in vitroassay for quantitating the invasive potential of tumor cells. Cancer Res, 47, 3239–45.
Kimata K, Okayama M, Oohira A and Suzuki S, 1974, Heterogeneity of proteochondroitin sulfates produced by chondrocytes at different stages of cytodifferentiation. J Biol Chem, 249, 1646–53.
Samlowski WE, Robertson BA, Draper BK, Prystas E and McGregor JR, 1991, Effect of supravital fluorochromes used to analyze the in vivohoming of murine lymphocytes on cellular function. J Immunol Meth, 144, 101–5.
Saiki I, Murata J, Iida J, Nishi N, Sugimura K and Azuma I, 1989, The inhibition of murine lung metastasis by synthetic polypeptides [poly(arg-gly-asp) and poly(tyr-ile-gly-ser-arg)] with a core sequence of cell adhesion molecules. Brit J Cancer, 59, 194–7.
Saiki I, Murata J, Matsuno M, et al. 1990, Antimetastatic and anti-invasive effects of polymeric Arg-Gly-Asp (RGD) peptide, poly (RGD), and its analogues. Jap J Cancer Res, 81, 660–7.
Murata J, Saiki I, Iida J, et al. 1989, Inhibition of tumor cell adhesion by anti-metastatic polypeptide containing a repetitive Arg-Gly-Asp sequence. Int J Macromol, 11, 226–32. 1 1 1
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Karasawa, K., Sugiura, N., Hori, Y. et al. Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity. Clin Exp Metastasis 15, 83–93 (1997). https://doi.org/10.1023/A:1018488424119
Issue Date:
DOI: https://doi.org/10.1023/A:1018488424119