Skip to main content
Log in

SPARC Modulates Cell Growth, Attachment and Migration of U87 Glioma Cells on Brain Extracellular Matrix Proteins

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

We have identified secreted protein acidic and rich in cysteine (SPARC) as a potential glioma invasion-promoting gene. To determine whether SPARC alters the growth, attachment, or migration of gliomas, we have used U87T2 and doxycycline-regulatable SPARC-transfected clones to examine the effects of SPARC on (1) cell growth, (2) cell cycle progression, (3) cell attachment, and (4) cell migration, using growth curves, flow cytometry, attachment, and migration analyses on different brain ECMs, including collagen IV, laminin, fibronectin, vitronectin, hyaluronic acid, and tenascin. Our data indicate that SPARC delays tumor cell growth in the log phase of the growth curve. The clones secreted different levels of SPARC. The clone secreting the lowest level of SPARC was associated with a higher percentage of cells in G2M, whereas the clones secreting the higher levels of SPARC were associated with a greater percentage of cells in G0/G1. In comparison to the parental U87T2 clone, the SPARC-transfected clones demonstrated increased attachment to collagen, laminin, hyaluronic acid, and tenascin, but not to vitronectin or fibronectin. SPARC-transfected clones also demonstrated altered migration on the different extracellular matrix proteins. The modulation of migration, either positive or negative, was associated with changes in the level of secreted SPARC. These data suggest that SPARC may modulate glioma proliferation and invasion by modulating both the growth and migration of glioma cells.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lane TE, Sage EH: The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB 8: 163–173, 1994

    Google Scholar 

  2. Sage EH: Terms of attachment: SPARC and tumorigenesis. Nat Med 3: 144–146, 1997

    Google Scholar 

  3. Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR: Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26, 99–105, 1981

    Google Scholar 

  4. Sage H, Johnson C, Bornstein P: Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem 259: 3993–4007, 1984

    Google Scholar 

  5. Lane TF, Sage EH: Functional mapping of SPARC peptides from two distinct sites modulate cell adhesion. J Cell Biol 111: 3065–3076, 1990

    Google Scholar 

  6. Mayer U, Aumailley M, Mann K, Timpl R, Engel J: Calcium-dependent binding of basement membrane protein BM-40 (osteonectin, SPARC) to basement membrane collagen Type IV. E J Biochem 198: 141–150, 1991

    Google Scholar 

  7. Rosenblatt S, Bassuk JA, Alpers CE, Sage EH, Timpl R, Preissner KT: Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: Characterization of the binding of vitronectin to osteonectin (BM40, SPARC). Biochem J 324: 311–319, 1997

    Google Scholar 

  8. Yost JC, Sage EH: Specific interaction of SPARC with endothelial cells is mediated through a carboxy-terminal sequence containing a calcium-binding E-F hand. J Biol Chem 268: 25790–25796, 1993

    Google Scholar 

  9. Motomed K, Sage EH: Regulation of vascular morphogenesis by the matricellular protein SPARC. Kidney Int 51: 1383–1387, 1997

    Google Scholar 

  10. Greenwood JA, Murphy-Ullrich JE: Signaling of de-adhesion in cellular regulation and motility. Microsc Res Tech 43: 420–432, 1998

    Google Scholar 

  11. Funk SE, Sage EH: The Ca++-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells. Proc Natl Acad Sci USA 88: 2648–2652, 1991

    Google Scholar 

  12. Funk SE, Sage EH: Differential effects of SPARC and cationic SPARC peptides on DNA synthesis by endothelial cells and fibroblasts. J Cell Physiol 154: 53–63, 1993

    Google Scholar 

  13. Sage EH, Bassuk JA, Yost JC, Folkman J, Lane TF: Inhibition of endothelial cell proliferation by SPARC is mediated through Ca2+-binding EF-hand sequence. L Cell Biochem 57: 127–140, 1995

    Google Scholar 

  14. Raines EW, Lane TF, Iruella-Arispe ML, Ross R, Sage EH: The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and-BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci USA 89: 1281–1285, 1992

    Google Scholar 

  15. Kupprion C, Motamed K, Sage EH: SPARC (BM40, Osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells. J Biol Chem 273: 29635–29640, 1998

    Google Scholar 

  16. Gooden MD, Vernon RB, Bassuk JA, Sage EH: Cell cycledependent nuclear localization of the matricellular protein SPARC: Association with the nuclear matrix. J Cell Biochem 74: 152–167, 1999

    Google Scholar 

  17. Rempel SA, Golembieski WA, Ge S, Lemke N, Elisevich K, Mikkelsen T, Gutiérrez JA: SPARC: A signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas. J Neuropathol Exp Neurol 57: 1112–1121, 1998

    Google Scholar 

  18. Rempel SA, Ge S, Gutiérrez JA: SPARC: A potential diagnostic marker of invasive meningiomas. Clin Cancer Res 5: 237–241, 1999

    Google Scholar 

  19. Vajkoczy P, Menger MD, Goldbrunner R, Ge S, Fong TAT, Vollmar B, Schilling L, Ullrich A, Hirth KP, Tonn JC, Schmiedek P, Rempel SA: Targeting angiogenesis inhibits glioma invasion and SPARC expression. Int J Cancer 87: 261–268, 2000

    Google Scholar 

  20. Golembieski WA, Ge S, Nelson K, Mikkelsen T, Rempel SA: Increased SPARC expression promotes U87 glioblastoma invasion in vitro. Int J Dev Neurosci 17: 463–472, 1999

    Google Scholar 

  21. Gladson CL, Cheresh DA: Glioblastoma expression of vitronectin and the alpha v beta 3 integrin: Adhesion mechanism for transformed glial cells. J Clin Invest 88: 1924–1932, 1991

    Google Scholar 

  22. Gladson CL, Wilcox JN, Sanders L, Gillespie GY, Cheresh DA: Cerebral microenvironment influences expression of the vitronectin gene in astrocytic tumors. J Cell Sci 108: 947–956, 1995

    Google Scholar 

  23. Giese A, Loo MA, Rief MD, Tran N, Berens ME: Substrates for astrocytoma invasion. Neurosurgery 37: 294–302, 1995

    Google Scholar 

  24. Menon PM, Gutiérrez JA, Rempel SA: A study of SPARC and vitronectin localization and expression in pediatric and adult gliomas: High SPARC expression correlates with decreased migration on vitronectin. Int J Oncol 17: 683–693, 2000

    Google Scholar 

  25. Berens ME, Rief MD, Loo MA, Giese A: The role of extracellular matrix in human astrocytoma migration and proliferation studied in a microliter scale assay. Clin Exp Metastasis 12: 405–415, 1994

    Google Scholar 

  26. Giese A, Rief MD, Loo MA, Berens ME: Determinants of human astrocytoma migration. Cancer Res 54: 3897–3904, 1994

    Google Scholar 

  27. Giese A, Westphal M: Glioma invasion of the central nervous system. Neurosurgery 39: 235–252, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rempel, S.A., Golembieski, W.A., Fisher, J.L. et al. SPARC Modulates Cell Growth, Attachment and Migration of U87 Glioma Cells on Brain Extracellular Matrix Proteins. J Neurooncol 53, 149–160 (2001). https://doi.org/10.1023/A:1012201300188

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012201300188

Navigation