Basic Research - Cancer(구연) (E-013)

Collagen type VI-alpha 1 and 2, novel tumor suppressors, repress proliferation, migration, and invasion of bladder cancer cells
충북대학교 의과대학 비뇨의학교실
서성필, 변영준, 박현미, 정필두, 강호원, 김원태, 김용준, 윤석중, 이상철, 김원재
Background: The bladder cancer (BCa) microenvironment comprises heterogeneous tumor cell populations, the surrounding stroma (which is populated by different types of mesenchymal cell), and the extracellular matrix (ECM). Collagen, the scaffold of the tumor microenvironment, regulates ECM remodeling to promote tumor infiltration, angiogenesis, invasion, and migration. Here, we examined how collagen type VI-alpha (COL6A) 1 and 2 function during BCa pathogenesis and progression. The aim is to facilitate precision therapeutics, risk stratification, and molecular diagnosis.
Methods: Expression of COL6A1 and COL6A2 mRNA in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) tissue samples was measured using real-time polymerase chain reaction. In addition, the tumor-suppressive effects of COL6A1 and COL6A2 in BCa EJ cells were assessed.
Results: Compared with normal controls, COL6A1 and COL6A2 were downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively); however, expression of miRNAs miR-6124 and miR-4651, which regulate COL6A1 and COL6A2, increased significantly (P<0.05). COL6A1 and COL6A2 effectively inhibited proliferation of EJ cells and induced cell cycle arrest at G1 phase. In addition, COL6A1 and COL6A2 played roles in MAPK and AKT signaling by increasing phosphorylation of p38 MAPK and reducing AKT phosphorylation. Finally, COL6A1 and COL6A2 inhibited wound healing and invasion by suppressing activity of matrix metalloproteinase (MMP)-2 and MMP-9.
Conclusion: COL6A1 and COL6A2 act as classical collagens by forming a physical barrier to BCa tumor growth and invasion.
keywords : collagen type VI-alpha, bladder cancer, pathogenesis, progression