Abstract
In this study, the levels of TNF-α and its soluble receptors sTNF-Rp55 and sTNF-Rp75 were analyzed in cocultures of human colon carcinoma cell spheroids prepared from different grades of tumors with normal human colon epithelium, myofibroblast, and endothelial cell monolayers. Additionally, the influence of exogenously added rhTGF-β1 (2 ng/ml) on the TNF-α and sTNF-Rs levels was tested. Direct interactions of colon carcinoma spheroids with normal cells caused decreases in TNF-α levels and normal cell-dependent changes in sTNF-Rs amounts as compared to normal cells cultured alone. The addition of rhTGF-β1 to the cocultures caused a significant increase in TNF-α levels with a simultaneous decrease in the amounts of both sTNF-Rs. During direct interactions of colon carcinoma cells with normal tissue, paracrine effects are very important. We showed that TGF-β1 acts synergistically with TNF-α and significantly limits sTNF-Rs shedding. Therefore, TNF-Rs bound to cellular membranes, but not their soluble forms, play an important role in tumor/normal cell interactions. TGF-β1 and sTNF-Rs, in turn, may be valuable factors in colon cancer development and metastasis.
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Editor: J. Denry Sato
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Paduch, R., Niedziela, P. TGF-β1 influence on TNF-α production and sTNF-Rs shedding in a coculture of colon carcinoma cell spheroids with normal cells. In Vitro Cell.Dev.Biol.-Animal 45, 371–377 (2009). https://doi.org/10.1007/s11626-009-9190-9
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DOI: https://doi.org/10.1007/s11626-009-9190-9