Skip to main content
Log in

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Poste G and Fidler IJ, 1980, The pathogenesis of cancer metastasis. Nature, 283283, 139–46.

    Google Scholar 

  2. Vlodavsky I and Gospodarowicz D, 1981, Respective roles of laminin and fibronectin in adhesion of human carcinoma and sarcoma cells. Nature, 289, 304–6.

    Google Scholar 

  3. 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.

    Google Scholar 

  4. 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.

    Google Scholar 

  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.

    Google Scholar 

  6. 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.

    Google Scholar 

  7. 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.

    Google Scholar 

  8. 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.

    Google Scholar 

  9. 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.

    Google Scholar 

  10. Iwamoto Y, Robey FA, Graf J, et al. 1987, YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science, 238, 1132–4.

    Google Scholar 

  11. 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.

    Google Scholar 

  12. 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.

    Google Scholar 

  13. 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.

    Google Scholar 

  14. 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.

    Google Scholar 

  15. 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.

    Google Scholar 

  16. 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.

    Google Scholar 

  17. 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.

    Google Scholar 

  18. 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.

    Google Scholar 

  19. 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.

    Google Scholar 

  20. 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.

    Google Scholar 

  21. 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.

    Google Scholar 

  22. 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.

    Google Scholar 

  23. 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.

    Google Scholar 

  24. 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.

    Google Scholar 

  25. Fidler IJ, 1973, Selection of successive tumour lines for metastasis. Nature, 242, 148–9.

    Google Scholar 

  26. Ruoslahti E, Hayman EG, Pierschbacher M and Engvall E, 1982, Fibronectin: purification, immunochemical properties, and biological activities. Meth Enzymol, 82, 803–31.

    Google Scholar 

  27. 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.

    Google Scholar 

  28. 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.

    Google Scholar 

  29. 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.

    Google Scholar 

  30. 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.

    Google Scholar 

  31. 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.

    Google Scholar 

  32. 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints 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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018488424119

Navigation