Effects of Cytokines on the Epithelial to Mesenchymal Transition in Renal Cell Carcinoma

Abstract

Kidney cancer presents in many different forms, some more aggressive than others. Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, may undergo an epithelial to mesenchymal transition (EMT) where cells become elongated and spindly and metastasize. There is evidence in other cancer types, that EMT may also lead to changes in immunogenicity of the tumor, including upregulation of immune checkpoint inhibitors such as PD-L1. When cells undergo EMT, various transcription factors are upregulated or downregulated by environmental conditions and cytokines. This study explores the effects of hypoxia, hepatocyte growth factor (HGF), interferon-γ (IFN-γ), and transforming growth factor-beta (TGFβ) on EMT and PD-L1 expression in 786-O and Caki-1 clear cell carcinoma cell lines. Protein level analysis was conducted using cell cultures and Western blotting techniques. Results indicated that the presence of cytokines and hypoxia, both individually and together, play important roles in the induction of EMT in ccRCC and in regulation of PD-L1. Understanding the genetic mechanisms of EMT and its effects on the immune microenvironment can aid in the development of promising cancer treatment and prevention methods for the future.