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Published on: October 27, 2020
Transforming growth factors β and their signaling pathway in renal cell carcinoma and peritumoral space-transcriptome
Dariusz Kajdaniuk1, Dorota Hudy2, Joanna Katarzyna Strzelczyk2
1Department 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. dkajdaniuk@sum.edu.pl.
Purpose:
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?.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Gene expression in the transforming growth factor beta (TGFβ)/Smads pathway is altered in kidney cancer. This dysregulation in tumor and microenvironment tissues impacts cancer aggressiveness and spread.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The transforming growth factor beta (TGFβ)/Smads pathway plays a crucial role in cellular processes.
- Dysregulation of this pathway is implicated in various cancers, including renal cell carcinoma (RCC).
- Understanding gene expression patterns in tumor and surrounding tissues is vital for cancer research.
Purpose of the Study:
- To investigate the involvement of TGFβ1-3, their receptors (TGFβRI-III), and Smad1-7 proteins in kidney cancer pathogenesis.
- To analyze the gene expression of the TGFβ/Smads pathway in RCC tissues, tumor microenvironment (TME), and normal kidney (NK) tissue.
Main Methods:
- Molecular analysis of kidney tissue samples from 20 RCC patients.
- Quantification of mRNA expression using quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Main Results:
- TGFβ/Smads pathway gene expression is dysregulated in both RCC and TME tissues.
- TGFβ1 and TGFβ3 showed increased expression in TME compared to NK tissues.
- Several genes, including TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6, were underexpressed in RCC compared to TME and NK tissues.
Conclusions:
- Underexpression of TGFβ signaling genes in RCC may lead to reduced antiproliferative and pro-apoptotic effects.
- Overexpression in the TME likely contributes to an immunosuppressive environment and affects non-neoplastic cells.
- TME characteristics, influenced by TGFβ/Smads pathway genes, may determine tumor aggressiveness and metastatic potential.
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