The Role of Regnase-1 Protein in Sculpting of Tumor Microenvironment

Abstract

The tumor microenvironment (TME) contains cancer-associated fibroblasts (CAFs) and their tumor-supportive role helps to build an environment in favor of cancer cell progression. Recent researches have revealed that targeting the tumor microenvironment, as well as the cancer cells, inhibits cancer progression far more effectively, while also overcoming the development of drug resistance. Macrophage polarization also helps cancer cells transform the microenvironment into a pro-tumoral environment. In previous studies, Gunaydin et al. have shown that CAFs play a major role in shaping the TME, thereby inducing the accumulation of monocytes in the TME and their differentiation into M2-like macrophages, enabling them to transform into a subtype that can perform immunosuppressive functions. However, the mechanisms underlying monocyte accumulation in the TME of CAFs are not yet known. The fact that Regnase-1 (MCP-1 Induced Protein) is induced by MCP-1, the major regulator of monocyte recruitment, and control in inflammatory processes prompted us to investigate the effects of this protein on monocyte recruitment by CAFs to the TME. In this study, α-SMA (α-smooth muscle actin) positive CAFs were obtained from patients with breast tumors and Regnase-1 protein expression in these cells was investigated. According to our study results, it was observed that CAFs obtained from breast tumors expressed Regnase-1 and MCP-1 protein. Our study results showed that there is a statistically significant correlation between MCP-1 and Regnase-1 protein expressions in CAFs, as well as between these protein expressions and CAF grade.