Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1985 Apr 1;100(4):1041–1049. doi: 10.1083/jcb.100.4.1041

An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells

PMCID: PMC2113750  PMID: 3156864

Abstract

Heparan sulfate was isolated form the cell surface, cell pellet, and culture medium of exponentially growing as well as postconfluent bovine aortic smooth muscle cells (SMCs). After chromatography on DEAE- Sephadex and Sepharose 4B, the various mucopolysaccharides were examined for their ability to cause growth inhibition in a SMC bioassay. The heparan sulfate isolated from the surface of postconfluent SMCs possessed approximately eight times the antiproliferative potency per cell of the heparan sulfate obtained from the surface of exponentially growing SMCs. Heparan sulfate isolated from other fractions of exponentially growing or postconfluent SMCs possesses little growth inhibitory activity. The difference in the antiproliferative activities of heparan sulfate obtained from the surface of SMCs in the two growth states could not be attributed to the synthesis of a greater mass of mucopolysaccharide by postconfluent SMCs. Indeed, heparan sulfate isolated from the surface of the postconfluent SMCs exhibits a specific antiproliferative activity which is 13-fold greater than mucopolysaccharide obtained from the surface of exponentially growing SMCs and more than 40-fold greater than commercially available heparin. In addition, exponentially growing SMCs did not exhibit an enhanced ability to degrade the complex carbohydrate. Furthermore, other investigations indicate that the small amount of growth inhibitory activity intrinsic to heparan sulfate isolated from the surface of exponentially growing SMCs is due to residual, biologically active, mucopolysaccharide produced by the primary postconfluent SMCs from which the exponentially growing SMCs were derived. These studies suggest that bovine aortic SMCs are capable of controlling their own growth by the synthesis of a specific form of heparan sulfate with antiproliferative potency.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernanke D. H., Markwald R. R. Effects of hyaluronic acid on cardiac cushion tissue cells in collagen matrix cultures. Tex Rep Biol Med. 1979;39:271–285. [PubMed] [Google Scholar]
  2. Bowen-Pope D. F., Ross R. Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem. 1982 May 10;257(9):5161–5171. [PubMed] [Google Scholar]
  3. Castellot J. J., Jr, Addonizio M. L., Rosenberg R., Karnovsky M. J. Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth. J Cell Biol. 1981 Aug;90(2):372–379. doi: 10.1083/jcb.90.2.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Castellot J. J., Jr, Beeler D. L., Rosenberg R. D., Karnovsky M. J. Structural determinants of the capacity of heparin to inhibit the proliferation of vascular smooth muscle cells. J Cell Physiol. 1984 Sep;120(3):315–320. doi: 10.1002/jcp.1041200309. [DOI] [PubMed] [Google Scholar]
  5. Chamley-Campbell J., Campbell G. R., Ross R. The smooth muscle cell in culture. Physiol Rev. 1979 Jan;59(1):1–61. doi: 10.1152/physrev.1979.59.1.1. [DOI] [PubMed] [Google Scholar]
  6. Clowes A. W., Karnowsky M. J. Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature. 1977 Feb 17;265(5595):625–626. doi: 10.1038/265625a0. [DOI] [PubMed] [Google Scholar]
  7. Comper W. D., Laurent T. C. Physiological function of connective tissue polysaccharides. Physiol Rev. 1978 Jan;58(1):255–315. doi: 10.1152/physrev.1978.58.1.255. [DOI] [PubMed] [Google Scholar]
  8. Culp L. A., Murray B. A., Rollins B. J. Fibronectin and proteoglycans as determinants of cell-substratum adhesion. J Supramol Struct. 1979;11(3):401–427. doi: 10.1002/jss.400110314. [DOI] [PubMed] [Google Scholar]
  9. DiCorleto P. E., Gajdusek C. M., Schwartz S. M., Ross R. Biochemical properties of the endothelium-derived growth factor: comparison to other growth factors. J Cell Physiol. 1983 Mar;114(3):339–345. doi: 10.1002/jcp.1041140313. [DOI] [PubMed] [Google Scholar]
  10. Guyton J. R., Rosenberg R. D., Clowes A. W., Karnovsky M. J. Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin. Circ Res. 1980 May;46(5):625–634. doi: 10.1161/01.res.46.5.625. [DOI] [PubMed] [Google Scholar]
  11. Heldin C. H., Westermark B., Wasteson A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664–3668. doi: 10.1073/pnas.78.6.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoover R. L., Rosenberg R., Haering W., Karnovsky M. J. Inhibition of rat arterial smooth muscle cell proliferation by heparin. II. In vitro studies. Circ Res. 1980 Oct;47(4):578–583. doi: 10.1161/01.res.47.4.578. [DOI] [PubMed] [Google Scholar]
  13. Linker A., Hovingh P. The uses of degradative enzymes as tools for identification and structural analysis of glycosaminoglycans. Fed Proc. 1977 Jan;36(1):43–46. [PubMed] [Google Scholar]
  14. Marcum J. A., McKenney J. B., Rosenberg R. D. Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium. J Clin Invest. 1984 Aug;74(2):341–350. doi: 10.1172/JCI111429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marcum J. A., Rosenberg R. D. Anticoagulantly active heparin-like molecules from vascular tissue. Biochemistry. 1984 Apr 10;23(8):1730–1737. doi: 10.1021/bi00303a023. [DOI] [PubMed] [Google Scholar]
  16. Martin B. M., Gimbrone M. A., Jr, Unanue E. R., Cotran R. S. Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. J Immunol. 1981 Apr;126(4):1510–1515. [PubMed] [Google Scholar]
  17. Olson E. N., Glaser L., Merlie J. P., Lindstrom J. Expression of acetylcholine receptor alpha-subunit mRNA during differentiation of the BC3H1 muscle cell line. J Biol Chem. 1984 Mar 10;259(5):3330–3336. [PubMed] [Google Scholar]
  18. Oosta G. M., Favreau L. V., Beeler D. L., Rosenberg R. D. Purification and properties of human platelet heparitinase. J Biol Chem. 1982 Oct 10;257(19):11249–11255. [PubMed] [Google Scholar]
  19. Ross R., Glomset J. A. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science. 1973 Jun 29;180(4093):1332–1339. doi: 10.1126/science.180.4093.1332. [DOI] [PubMed] [Google Scholar]
  20. Ross R., Glomset J., Kariya B., Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. doi: 10.1083/jcb.50.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rutherford R. B., Ross R. Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate. J Cell Biol. 1976 Apr;69(1):196–203. doi: 10.1083/jcb.69.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stemerman M. B., Ross R. Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. J Exp Med. 1972 Oct 1;136(4):769–789. doi: 10.1084/jem.136.4.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Strauch A. R., Rubenstein P. A. Induction of vascular smooth muscle alpha-isoactin expression in BC3H1 cells. J Biol Chem. 1984 Mar 10;259(5):3152–3159. [PubMed] [Google Scholar]
  25. Vogel K. G., Kendall V. F., Sapien R. E. Glycosaminoglycan synthesis and composition in human fibroblasts during in vitro cellular aging (IMR-90). J Cell Physiol. 1981 May;107(2):271–281. doi: 10.1002/jcp.1041070214. [DOI] [PubMed] [Google Scholar]
  26. Whittenberger B., Raben D., Lieberman M. A., Glaser L. Inhibition of growth of 3T3 cells by extract of surface membranes. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5457–5461. doi: 10.1073/pnas.75.11.5457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Williams L. T., Tremble P., Antoniades H. N. Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5867–5870. doi: 10.1073/pnas.79.19.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES