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Effects of transforming growth factor beta1 expression in a rat colon carcinoma : growth inhibition, leukocyte infiltration and production of interleukin-10 and tumor necrosis factor alpha

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Author

Summary, in English

The cytokine transforming growth factor beta-1 (TGFbeta1), was transfected into a TGFbeta1-negative rat colon carcinoma. The growth of isografts of TGFbeta1-expressing tumors was compared to that of vector control transfectants. The TGFbeta1 transfectant grew significantly more slowly after intrahepatic isografting than did vector control and wild-type tumors. The TGFbeta1-transfected tumor tissue had significantly greater infiltration of both CD4+ and CD8+ T lymphocytes than did the vector control tumor. The tumor-infiltrating leukocytes (TIL) from TGFbeta1-transfected tumor secreted significantly more of the cytokines interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFalpha) than did TIL from the vector control tumor. The TGFbeta1 transfectant also demonstrated a significantly slower outgrowth in immunodeficient SCID mice, supporting a non-T-lymphocyte-dependent mechanism for the tumor retardation. In SCID mice, the TGFbeta1-transfected tumor demonstrated significantly greater infiltration of both granulocytes and macrophages than did the vector control transfectant. We also demonstrated a direct inhibitory effect of rat TNFalpha on tumor proliferation in vitro. These results suggest that TGFbeta1 induces a local secretion of immunomodulating cytokines and that this may influence monocytes, lymphocytes and granulocytes to retard tumor outgrowth.

Publishing year

2000-01

Language

English

Pages

579-587

Publication/Series

Cancer Immunology and Immunotherapy

Volume

48

Issue

10

Document type

Journal article

Publisher

Springer

Topic

  • Cancer and Oncology

Keywords

  • Animals
  • Carcinoma
  • Cell Movement
  • Chimera
  • Colonic Neoplasms
  • Cytokines
  • Growth Inhibitors
  • Interleukin-10
  • Lymphocytes, Tumor-Infiltrating
  • Mice
  • Mice, SCID
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred WF
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, Non-U.S. Gov't

Status

Published

Research group

  • Experimental Pathology, Malmö
  • Brain function and behavioral mechanisms in psychopathology

ISBN/ISSN/Other

  • ISSN: 1432-0851