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Effects of growth factors on the antiproliferative activity of tumor necrosis factors

B J Sugarman, G D Lewis, T E Eessalu

    Cancer Research
    |February 1, 1987
    PubMed

    Insights

    Growth factors like epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) can interfere with the anti-tumor effects of tumor necrosis factors (TNFs). This interference suggests growth factors may promote tumor growth by aiding cell proliferation and hindering immune defense mechanisms.

    Area of Science:

    • Immunology
    • Cell Biology
    • Oncology

    Background:

    • Tumor necrosis factors (TNFs) are cytokines crucial for host defense against tumor progression.
    • Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are known to influence cell proliferation.
    • The interaction between growth factors and TNF-mediated anti-tumor effects requires further investigation.

    Purpose of the Study:

    • To investigate the in vitro effects of EGF and TGF-alpha on the antiproliferative and cytotoxic actions of tumor necrosis factors (TNFs).
    • To determine if growth factors interfere with TNF-alpha and TNF-beta mediated inhibition of tumor cell growth.
    • To explore the mechanisms by which growth factors might influence TNF-alpha's efficacy against tumor cells.

    Main Methods:

    • Utilized human cervical carcinoma cell line (ME-180) and NIH 3T3 fibroblasts for in vitro experiments.
    • Assessed the antiproliferative effects of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) and -beta in the presence of EGF and rHuTGF-alpha.
    • Evaluated the impact of growth factors on TNF-alpha's cytotoxic effects and receptor binding affinity.

    Main Results:

    • EGF and rHuTGF-alpha inhibited the antiproliferative effects of rHuTNF-alpha and -beta on ME-180 cells, with effects observed at 100 pg/ml and maximal between 1-10 ng/ml.
    • The observed inhibition was specific to TNFs and not due to changes in TNF receptor downregulation or affinity.
    • TGF-beta also antagonized rHuTNF-alpha's cytotoxic effects on NIH 3T3 fibroblasts, independent of enhanced cell proliferation.

    Conclusions:

    • Growth factors like EGF and TGF-alpha can interfere with the anti-tumor activity of TNFs in vitro.
    • These findings suggest that growth factors may contribute to tumor progression in vivo.
    • Potential mechanisms include autocrine stimulation of tumor cell growth and interference with host defense mechanisms.

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