Mechanisms by which interleukin-6 attenuates cell invasion and tumorigenesis in human bladder carcinoma cells.

Abstract

Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN), N-myc downstream gene 1 (NDRG1), and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

• Authors: Ke-Hung Tsui, Shyi-Wu Wang, Li-Chuan Chung, Tsui-Hsia Feng, Tzu-Yi Lee, Phei-Lang Chang, Horng-Heng Juang
• Journal: BioMed research international (Biomed Res Int) Vol. 2013 Pg. 791212 ( 2013) ISSN: 2314-6141 [Electronic] United States
• PMID: 23762858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD82 protein, human
• Cadherins
• Cell Cycle Proteins
• IL6 protein, human
• Interleukin-6
• Intracellular Signaling Peptides and Proteins
• Kangai-1 Protein
• N-myc downstream-regulated gene 1 protein
• SERPIN-B5
• Serpins
• Vimentin

Topics

• Animals
• Cadherins (genetics, metabolism)
• Carcinogenesis (genetics, metabolism, pathology)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-6 (metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Kangai-1 Protein (genetics, metabolism)
• Mice
• Mice, Nude
• Neoplasm Invasiveness
• Serpins (genetics, metabolism)
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)
• Vimentin (metabolism)