Abstract
In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1β in RCC. We found that IL-1β stimulates substantial monocyte chemoattractant protein (MCP)-1 production in RCC cells by activating NF-kB and AP-1. In our xenograft RCC model, intra-tumoral MCP-1 injection down-regulated Ki67 expression and reduced tumor size. Microarray analysis revealed that MCP-1 treatment altered protein-folding processes in RCC cells. MCP-1-treated RCC cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) and molecules involved in endoplasmic reticulum (ER) stress-mediated apoptosis, namely C/EBP Homologous Protein (CHOP), protein kinase-like ER kinase (PERK), and calnexin (CNX). ER stress-mediated apoptosis in MCP-1-treated RCC cells was confirmed using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Moreover, ectopic MCPIP expression increased PERK expression in Human embryonic kidney (HEK)293 cells. Our meta-analysis revealed that low MCP-1 levels reduce 1-year post-nephrectomy survival in patients with RCC. Immunohistochemistry indicated that in some RCC biopsy samples, the correlation between MCP-1 or MCPIP expression and tumor stages was inverse. Thus, MCP-1 and MCPIP potentially reduce the IL-1β-mediated oncogenic effect in RCC; our findings suggest that ER stress is a potential RCC treatment target.
Highlights
Renal cell carcinoma (RCC) is one of the 10 most common cancers in both men and women, with the third highest incidence among urological malignancies
Western blotting analysis demonstrated that monocyte chemoattractant protein-1 (MCP-1)-induced protein (MCPIP)-1 protein levels decreased at 0.5 and 1 h and substantially increased at 1.5 h and beyond, reaching a peak at 36 h of monocyte chemoattractant protein (MCP)-1 treatment. (Figure 2F). These results indicate that IL-1β induces the production of MCP-1; MCP-1 enhances MCPIP-1 expression in RCC cells in an autIontc. rJ.iMneol.mScia. 2n0n19e, 2r0.,T61h01e results suggest that the MCP-1/MCPIP-1 signaling path5wofa1y8 may be established in RCC cells in response to elevated levels of IL-1β
We investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis involved in the events induced by MCP-1/MCPIP-1 signaling in RCC cells by analyzing the expression of C/EBP Homologous Protein (CHOP) and CNX
Summary
Renal cell carcinoma (RCC) is one of the 10 most common cancers in both men and women, with the third highest incidence among urological malignancies. A comprehensive genome-wide analysis highlighted the importance of genes participating in cellular metabolism, oxygen sensing, such as von Hippel–Lindau (VHL)/ Hypoxia-inducible factor (HIF) and PI3K/AKT pathways, as well as the maintenance of chromatin states, such as Polybromo (PBRM) I and SET domain-containing protein (SETD) 2, in ccRCC [3] This implied that ccRCC development and progression may be driven by oncogenic–metabolic shifts and epigenetic reprogramming. MCPIP-1 possesses transcriptional activity and its expression induces genes involved in ER stress and apoptosis in both human embryonic kidney HEK 293 cells and the cardiomyoblast cells These findings suggest that despite the oncogenicity caused by macrophage recruitment, MCP-1 may induce RCC cell apoptosis and exert an anti-cancer effect
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
