Papel do receptor 1 do TNF-α na proliferação celular e elementos estromais da próstata de camundongos submetidos à carcinogênese

Abstract

In the literature, TNF-α receptor 1 is related with a paradoxical action in prostate carcinogenesis: apoptosis/death or cell proliferation/survival. Therefore, it is important to clarify its real effect on this type of cancer by using an TNFR-1 knockout model, which was the purpose of this study. In this regard, the induction of prostatic carcinogenesis in mice C57bl/6 wild type (SM) and TNFR-1 knockout (KO) was performed with the carcinogen N-nitroso-N-methylurea (MNU) in a single dose followed by weekly doses of testosterone for six months, using mineral oil as a vehicle. The control group received only weekly doses of mineral oil. As a result of this induction, mice developed several types of lesions, where the control group presented only benign lesions, while MNU treated group presented benign and malignant lesions. Malignant lesions were more incidental in SM animals than in KO ones, suggesting that there is a proliferation/survival relationship when TNF-α binds to its receptor 1. This is consistent with the findings regarding cell proliferation that was higher in SM than in KO animals. In relation to the prostate stromal compartment, we found that there was no collagen alteration between the evaluated groups, however, there was an increase in fibronectin distribution in KO mice, in both the control and the carcinogenesis group. These data indicate a low stromal remodeling process in this group, which justifies the lower incidence of knockout cancer. Therefore, when it binds to its receptor 1, the cytokine TNF-α acts to promote cell proliferation and survival and the expression of fibronectin, activities which can favour prostate cancer progression in mice.