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

Research output: Contribution to journalArticle

Abstract

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.

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Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • 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
Original languageEnglish
Pages (from-to)579-587
Number of pages9
JournalCancer Immunology and Immunotherapy
Volume48
Issue number10
Publication statusPublished - 2000 Jan
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Genetics (Closed 2011) (011005100), Neurosurgery (013026000), Faculty of Medicine (000022000), Division IV (013230800)