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Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion.

Publication ,  Journal Article
Sampson, JH; Ashley, DM; Archer, GE; Fuchs, HE; Dranoff, G; Hale, LP; Bigner, DD
Published in: Neurosurgery
December 1997

OBJECTIVE: The promise of immunotherapies developed against brain tumors in animal models has not been realized in human clinical trials. This may be because of the routine use of rodent tumors artificially induced by chemicals or viruses that do not accurately portray the intrinsic qualities of spontaneously arising human tumors and that often fail to incorporate the role of immunosuppressants, such as transforming growth factor-beta, that are secreted by human gliomas. From an astrocytoma that arose spontaneously in inbred VM/Dk mice, we have characterized a highly tumorigenic spontaneous murine astrocytoma cell line (SMA-560) that retains features of glial differentiation and naturally produces high levels of biologically active transforming growth factor-beta. We have used this model to determine whether cytokine production by tumor cells will inhibit intracerebral astrocytoma growth. METHODS: Packaging cell lines producing replication-incompetent retroviral vectors were used to transfect the SMA-560 cell line in vitro with the genes encoding the murine cytokines interleukin (IL)-2, IL-3, IL-4, IL-6, tumor necrosis factor-alpha, gamma-interferon, or granulocyte-macrophage colony-stimulating factor or the costimulatory molecule B7.1 (CD80). RESULTS: Mice challenged intracerebrally with 5000 untransfected SMA-560 cells all succumbed to tumor within 30 days, with a median survival of 25 days. In contrast, mice challenged with SMA-560 cells producing IL-2, IL-4, or tumor necrosis factor-alpha each had a more than 400% increase in median survival (P < 0.0001). In these groups, 78.3% (18 of 23 mice), 66.7% (10 of 15 mice), and 60% (6 of 10 mice) of the mice, respectively, remained alive without evidence of tumor for longer than 100 days after the initial tumor challenge. All other cytokines tested and the expression of B7.1 failed to result in an increase in median survival. CONCLUSION: Using a spontaneous astrocytoma model in an inbred mouse strain, we have shown that cytokine production by glial tumors can abrogate their tumorigenicity in vivo despite production of transforming growth factor-beta. These results predict that approaches directed at cytokine production within intracerebral astrocytomas may be efficacious in human trials and that the "immunological privilege" of the brain may not be absolute under such conditions.

Duke Scholars

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

December 1997

Volume

41

Issue

6

Start / End Page

1365 / 1372

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • Retroviridae
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Immunohistochemistry
  • Histocompatibility Antigens Class I
  • Genetic Vectors
 

Citation

APA
Chicago
ICMJE
MLA
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Sampson, J. H., Ashley, D. M., Archer, G. E., Fuchs, H. E., Dranoff, G., Hale, L. P., & Bigner, D. D. (1997). Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion. Neurosurgery, 41(6), 1365–1372. https://doi.org/10.1097/00006123-199712000-00024
Sampson, J. H., D. M. Ashley, G. E. Archer, H. E. Fuchs, G. Dranoff, L. P. Hale, and D. D. Bigner. “Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion.Neurosurgery 41, no. 6 (December 1997): 1365–72. https://doi.org/10.1097/00006123-199712000-00024.
Sampson JH, Ashley DM, Archer GE, Fuchs HE, Dranoff G, Hale LP, et al. Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion. Neurosurgery. 1997 Dec;41(6):1365–72.
Sampson, J. H., et al. “Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion.Neurosurgery, vol. 41, no. 6, Dec. 1997, pp. 1365–72. Pubmed, doi:10.1097/00006123-199712000-00024.
Sampson JH, Ashley DM, Archer GE, Fuchs HE, Dranoff G, Hale LP, Bigner DD. Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion. Neurosurgery. 1997 Dec;41(6):1365–1372.
Journal cover image

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

December 1997

Volume

41

Issue

6

Start / End Page

1365 / 1372

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • Retroviridae
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Immunohistochemistry
  • Histocompatibility Antigens Class I
  • Genetic Vectors