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Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.

Publication ,  Journal Article
Ashley, DM; Sampson, JH; Archer, GE; Hale, LP; Bigner, DD
Published in: J Neuroimmunol
June 1, 1998

We have previously reported that local secretion of either TNF-alpha or TGF beta1 by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate tumor growth in mice. However, the use of TNF-alpha, while improving the overall survival of tumor bearing animals, was associated with early toxic deaths due to cerebral edema. In the present study, we demonstrate that TNF-alpha induces apoptosis of the SMA 560 cell line, as does TGF beta1, and that these two cytokines act in an additive fashion to enhance apoptosis and thus, to inhibit SMA 560 cell growth in vitro. Next, we show that the production of TGF beta1 when added to TNF-alpha production by central nervous system tumors in vivo abrogates any early deaths seen due to TNF-alpha toxicity and leads to a larger percentage of animals surviving CNS tumor challenge. Finally, we demonstrate that the production of TGF beta1 by tumor cells is associated with the abolition of tumor-associated cerebral edema in both TNF-alpha and in non-TNF-alpha producing tumors. These results are important for the development of effective and less toxic therapies for brain tumors, as well as for examining the pathogenesis of tumor-related cerebral edema.

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Published In

J Neuroimmunol

DOI

ISSN

0165-5728

Publication Date

June 1, 1998

Volume

86

Issue

1

Start / End Page

46 / 52

Location

Netherlands

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Survival Analysis
  • Retroviridae Infections
  • Retroviridae
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Lac Operon
 

Citation

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Ashley, D. M., Sampson, J. H., Archer, G. E., Hale, L. P., & Bigner, D. D. (1998). Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model. J Neuroimmunol, 86(1), 46–52. https://doi.org/10.1016/s0165-5728(98)00017-4
Ashley, D. M., J. H. Sampson, G. E. Archer, L. P. Hale, and D. D. Bigner. “Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.J Neuroimmunol 86, no. 1 (June 1, 1998): 46–52. https://doi.org/10.1016/s0165-5728(98)00017-4.
Ashley DM, Sampson JH, Archer GE, Hale LP, Bigner DD. Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model. J Neuroimmunol. 1998 Jun 1;86(1):46–52.
Ashley, D. M., et al. “Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.J Neuroimmunol, vol. 86, no. 1, June 1998, pp. 46–52. Pubmed, doi:10.1016/s0165-5728(98)00017-4.
Ashley DM, Sampson JH, Archer GE, Hale LP, Bigner DD. Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model. J Neuroimmunol. 1998 Jun 1;86(1):46–52.
Journal cover image

Published In

J Neuroimmunol

DOI

ISSN

0165-5728

Publication Date

June 1, 1998

Volume

86

Issue

1

Start / End Page

46 / 52

Location

Netherlands

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Survival Analysis
  • Retroviridae Infections
  • Retroviridae
  • Neurology & Neurosurgery
  • Mice, Inbred Strains
  • Mice
  • Lac Operon