Skip to main content
Log in

Glioma-stimulated chemoattraction of endothelial cells and fibroblastsin vitro: a model for the study of glioma-induced angiogenesis

  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Induction of angiogenesis is essential for the continued growth of solid tumors, and one critical component of tumor-induced angiogenesis involves the stimulation of microvascular cells to migrate into the growing mass. We have developed a convenient model system utilizing dual co-culture chambers to study cellular chemotaxis induced by glioma cellsin vitro. In this system, rat C6 glioma cells induced migration of fibroblasts and brain capillary endothelial cells. The migratory response was directly related to the number of C6 cells serving as stimulus in the lower chamber. Similar migratory responses were induced by C6 cell conditioned medium in a concentration dependent fashion. Medium conditioned by cultured human anaplastic astrocytoma cells was also found to contain potent chemotactic factor(s). This system may ultimately be employed in the identification of particular glioma cell population(s) and secreted factor(s) responsible for the chemoattraction of microvascular 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.

Similar content being viewed by others

References

  • Auerbach, R., Auerbach, W., Polakowski, I. (1991). Assays for angiogenesis: a review.Pharmac. Ther. 51:1–11.

    Article  Google Scholar 

  • Brem, S., Cotran, R., Folkman, J. (1972). Tumor Angiogenesis: A Quantitative Method for Histological Grading.J. Nat. Cancer. Ins. 48:2.

    Google Scholar 

  • Brem, H., Tamargo, R., Guerin, C., Brem, J., Brem, S. (1988). Brain Tumor Angiogeniesis. In Kornblith, P. L., Walker, M. D. (ed.),Advances in Neuro-Oncology, Future Publishing Company, Inc., New York, pp 89–120.

    Google Scholar 

  • Brem, S. (1977). The role of vascular proliferation in the growth of brain tumors.Clin. Neurosurg. 23:440–453.

    Google Scholar 

  • Burgess, W. H., Maciag, T. (1989). The heparin-binding (fibroblast) growth factor family of proteins.Ann. Rev Biochem. 58:575–606.

    Article  PubMed  Google Scholar 

  • Folkman, J., Klagsbrun, M. (1987). Angiogenic Factors.Science. 235:442–447.

    PubMed  Google Scholar 

  • Gimbrone, M.A., Leapman, S.B., Cotran, R.S., and Folkman, J. (1972). Tumor Dormancy In vivo by Prevention of Neovascularization.J. Exp. Med. 136:261–276.

    Article  PubMed  Google Scholar 

  • Heldin, C.H., Usuki, K., Miyazono, K. (1991). Platelet-derived endothelial cell growth factor.J. Cell. Biochem. 47:208–210.

    Article  PubMed  Google Scholar 

  • Hertig, A.T. (1935). Angiogenesis in the human placenta.Contrib. Embryol. 37:25–27.

    Google Scholar 

  • Ishikawa, F., Miyazono, K., Hellman, U., Hellman, U., Drexler, H., Wernstedt, C., Hagiwara, K., Usuki, K., Takaku, F., Risau, W., Heldin, C.H. (1989). Identification of angiogenic activity and the cloning and expression of platelet derived endothelial growth factor.Nature 338:557–562.

    Article  PubMed  Google Scholar 

  • Klagsbrun, M. (1991). Regulators of Angiogenesis: Stimulators, Inhibitors, and Extracellular Matrix.J. Cel. Biochem. 47:199–200.

    Article  Google Scholar 

  • Libermann, T.A., Friesel, R., Jaye, M., Lyall, R.M., Westermark, B., Drohan, W., Schmidt, A., Maciag T., Schlessinger, J. (1987). An angiogenic growth factor is expressed in human glioma cells.EMBO J. 6 (6):1627–1632.

    PubMed  Google Scholar 

  • Lobb, R.R., Alderman, E.M., Feet, J.W. (1985). Induction of angiogenesis by bovine derived class 1 heparin-binding growth factor.Biochem. 24:4969–4973.

    Article  Google Scholar 

  • Maxwell, M., Naber, S. P., Wolfe, H.J., Hedley-Whyte, E. T., Galanoppulos, T., Neville-Golden, J., Antoniades, H. N. (1991). Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression.Cancer. Res. 51:1345–1351.

    PubMed  Google Scholar 

  • Maxwell, M., Galanoppulos, T., Neville-Golden, J., Antoniades, H.N. (1992). Effect of the expression of transforming growth factor-ß2 in primary human glioblastomas on immunosuppression and loss of immune surveillance.J. Neurosurg. 76:799–804.

    PubMed  Google Scholar 

  • Morris, J. H. (1989). The Nervous System. in Cotran, R. S., Kumar, V., Robbins, S. L. (ed.)Robbins Pathologic Basis of Disease, Fourth Edition, W.B. Saunders Co., Philadelphia, pp. 1385–1450.

    Google Scholar 

  • Moscatelli, D., Marco, P., Rifkin, D.B. (1986). Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration.Proc. Natl. Acad. Sci. USA. 83:2091–2095.

    PubMed  Google Scholar 

  • Nister, M., Liebermann, T. A., Heldin, C.H., Westermark, B. (1988). Expression of Messenger RNAs for PDGF, TGFa, and their receptors in human malignant glioma cell lines.Cancer. Res. 48:3910–3918.

    PubMed  Google Scholar 

  • Nystrom, S. (1960). Pathological changes in blood vessels of human glioblastoma multiforme. Comparative studies using plastic casting, angiography, light microscopy and electron microscopy, and with reference to some other brain tumors.Acta. Pahtol. Microbiol. Scand. 49(suppl 137):1–83.

    Google Scholar 

  • Stefanik, D.F., Rizkalla, L.R., Soi, A., Golblatt, S.A., Razjalla, W.M. (1991). Acidic and basic fibroblast growth factors are present in glioblastoma multiforme.Cancer. Res. 51:5760–5765.

    PubMed  Google Scholar 

  • Thomas, K.A., Rios-Candelore, M., Gimenez-Gallego, G., DiSalvo, J., Bennett, C., Rodkey, J., Fitzpatrick, S. (1985). Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1.Proc. Natl. Acad. Sci. USA 82:6409–6413.

    PubMed  Google Scholar 

  • Wesseling, P., Vandersteenhoven, J.J., Downey, B.T., Ruiter, D.J., Burger, P.C. (1993) Cellular components of microvascular proliferation in human glial and metastatic brain neoplasms.Acta Neuropathol. 85:508–514.

    Article  PubMed  Google Scholar 

  • Westermark, B., Siegbahn, A., Heldin, C.H., Claesson-Welsh, L. (1990). B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase.Proc. Natl. Acad. Sci. USA. 87:128–132.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yassini, P.R., Stickler, D.L., Bloomfield, S.M. et al. Glioma-stimulated chemoattraction of endothelial cells and fibroblastsin vitro: a model for the study of glioma-induced angiogenesis. Metab Brain Dis 9, 391–399 (1994). https://doi.org/10.1007/BF02098885

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02098885

Key words

Navigation