MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis

Autor: Wei-Chun Chou, Shang-Chieh Lu, Hsuan-Lien Chung, Chiao-Yin Sun, Chun-Te Wu, Chia Huei Lee, Pin-Feng Hung, Shang-Lun Chiang
Rok vydání: 2019
Předmět:
0301 basic medicine
Protein Folding
interleukin-1β
medicine.medical_treatment
Interleukin-1beta
Apoptosis
urologic and male genital diseases
Mice
0302 clinical medicine
monocyte chemoattractant protein (MCP)-induced protein-1
Chemokine CCL2
Spectroscopy
TUNEL assay
Kinase
Chemistry
Interleukin
General Medicine
Endoplasmic Reticulum Stress
Prognosis
Kidney Neoplasms
female genital diseases and pregnancy complications
Neoplasm Proteins
Tumor Burden
Computer Science Applications
Gene Expression Regulation
Neoplastic
Cytokine
030220 oncology & carcinogenesis
Signal Transduction
renal cell carcinoma
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Ribonucleases
Cell Line
Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
neoplasms
Carcinoma
Renal Cell
Molecular Biology
Organic Chemistry
HEK 293 cells
Xenograft Model Antitumor Assays
030104 developmental biology
Terminal deoxynucleotidyl transferase
chemoattractant protein-1
Unfolded protein response
Cancer research
Transcription Factors
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 23
ISSN: 1422-0067
Popis: In renal cell carcinoma (RCC), interleukin (IL)-1&beta
may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1&beta
and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1&beta
in RCC. We found that IL-1&beta
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-1&beta
mediated oncogenic effect in RCC
our findings suggest that ER stress is a potential RCC treatment target.
Databáze: OpenAIRE
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