Collagen type VI‑α1 and 2 repress the proliferation, migration and invasion of bladder cancer cells
Xuan‐Mei Piao, Byung‐Doo Hwang, Pildu Jeong, Young Joon Byun, Ho Won Kang, Sung Wook Seo, Won Ho Kim, Jong‐Young Lee, Yun‐Sok Ha, Young-Suk Lee, Isaac Kim, Yung Hyun Choi, Eun‐Jong Cha, Sung‐Kwon Moon, Seok Hyun Yun, Wun‐Jae Kim
Abstract
The bladder cancer (BCa) microenvironment comprises heterogeneous tumor cell populations, the surrounding stroma and the extracellular matrix (ECM). Collagen, the scaffold of the tumor microenvironment, regulates ECM remodeling to promote tumor infiltration, angiogenesis, invasion and migration. The present study examined how collagen type VI‑α (COL6A) 1 and 2 function during BCa pathogenesis and progression, with the aim of facilitating the development of precision therapeutics, risk stratification and molecular diagnosis. <em>COL6A1</em> and <em>COL6A2</em> mRNA expression in non‑muscle invasive BCa (NMIBC) and MIBC tissue samples was measured using reverse transcription‑quantitative PCR. In addition, the tumor‑suppressive effects of <em>COL6A1</em> and <em>COL6A2</em> in human BCa EJ cells (MGH‑U1) were assessed. Compared with normal controls, <em>COL6A1</em> and <em>COL6A2</em> mRNA expression was downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively). <em>COL6A1</em> and <em>COL6A2</em> effectively inhibited the proliferation of human BCa EJ cells (MGH‑U1) and induced cell cycle arrest at the G<sub>1</sub> phase. Additionally, <em>COL6A1</em> and <em>COL6A2</em> served roles in MAPK and AKT signaling by increasing p38 MAPK phosphorylation and decreasing AKT phosphorylation. Finally, <em>COL6A1</em> and <em>COL6A2</em> inhibited wound healing and invasion by suppressing the activity of matrix metalloproteinase (MMP)‑2 and MMP‑9. In conclusion, COL6A1 and COL6A2 may act as classical collagens by forming a physical barrier to inhibit BCa tumor growth and invasion.