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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

Schiött, A LU ; Widegren, B LU ; Sjögren, H O LU ; Lindvall, M LU and C Johansson, Anna LU (2000) In Cancer Immunology and Immunotherapy 48(10). p.579-587
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... (More)

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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publication status
published
subject
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
in
Cancer Immunology and Immunotherapy
volume
48
issue
10
pages
9 pages
publisher
Springer
external identifiers
  • pmid:10630310
  • pmid:10630310
  • scopus:0033988217
ISSN
1432-0851
DOI
10.1007/PL00006676
language
English
LU publication?
yes
additional info
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)
id
dd2ec217-33b4-4e48-aa2e-a6fb0847f6e8 (old id 1117668)
date added to LUP
2016-04-01 15:35:02
date last changed
2022-01-28 06:05:35
@article{dd2ec217-33b4-4e48-aa2e-a6fb0847f6e8,
  abstract     = {{<p>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.</p>}},
  author       = {{Schiött, A and Widegren, B and Sjögren, H O and Lindvall, M and C Johansson, Anna}},
  issn         = {{1432-0851}},
  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}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{579--587}},
  publisher    = {{Springer}},
  series       = {{Cancer Immunology and Immunotherapy}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1007/PL00006676}},
  doi          = {{10.1007/PL00006676}},
  volume       = {{48}},
  year         = {{2000}},
}