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.
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.
Schiött
A
A
Department of Cell and Molecular Biology, Section of Tumor Immunology, University of Lund, Sweden. Asa.Schiott@wblab.lu.se
Johansson
A C
AC
Widegren
B
B
Sjögren
H O
HO
Lindvall
M
M
D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D002465:Cell Movement; D002678:Chimera; D003110:Colonic Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006131:Growth Inhibitors / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10