Department of Pathophysiology, Chair of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, H. Jordana 19, Zabrze, 41-808, Katowice, Poland.
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
Clin Transl Oncol. 2024 May;26(5):1229-1239. doi: 10.1007/s12094-023-03350-y. Epub 2023 Dec 12.
The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?.
Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR.
The study showed that the expression of the genes of TGFβ/Smads pathway is dysregulated in both RCC and the TME: TGFβ1, TGFβ3 expression is increased in the TME in comparison to the NK tissues; TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFβRI, TGFβRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues.
On the one hand, the underexpression of the TGFβ signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFβ/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.
本研究旨在验证以下假设：转化生长因子 TGFβ1-3、其受体 TGFβI-III 和细胞内信使蛋白 Smad1-7 是否参与肾癌的发病机制？TGFβ/Smads 通路的基因在肾细胞癌 (RCC) 组织、肿瘤周围组织 (TME；肿瘤微环境) 和正常肾脏 (NK) 组织中的表达情况如何？
将 20 名接受根治性肾切除术的 RCC 患者纳入分子分析。通过 RT-qPCR 定量检测基因的 mRNA 表达。
研究表明，TGFβ/Smads 通路的基因表达在 RCC 和 TME 中均失调：与 NK 组织相比，TME 中 TGFβ1、TGFβ3 的表达增加；与 TME 组织相比，RCC 中 TGFβ2、TGFβ3、TGFβRI、TGFβRIII、Smad1、Smad2、Smad3 和 Smad6 的表达下调；与 NK 组织相比，RCC 中 TGFβRI、TGFβRIII 和 Smad2 的表达下调。
一方面，恶性肿瘤中 TGFβ 信号通路基因的表达下调可能导致该细胞因子的抗增殖和促凋亡活性丧失。另一方面，TME 中 TGFβ/Smads 通路基因的过度表达高于肿瘤或 NK 组织，很可能导致肿瘤周围空间产生免疫抑制作用，并对 TME 中存在的非肿瘤细胞产生抗增殖和促凋亡作用。该区域的功能和形态一致性可能决定肿瘤的侵袭性以及肿瘤扩散的时间。
