Collagen type VI‑α1 and 2 repress the proliferation, migration and invasion of bladder cancer cells

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. COL6A1 and COL6A2 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 COL6A1 and COL6A2 in human BCa EJ cells (MGH-U1) were assessed. Compared with normal controls, COL6A1 and COL6A2 mRNA expression was downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively). COL6A1 and COL6A2 effectively inhibited the proliferation of human BCa EJ cells (MGH-U1) and induced cell cycle arrest at the G 1 phase. Additionally, COL6A1 and COL6A2 served roles in MAPK and AKT signaling by increasing p38 MAPK phosphorylation and decreasing AKT phosphorylation. Finally, COL6A1 and COL6A2 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.

An Integrated Bioinformatics Analysis towards the Identification of Diagnostic, Prognostic, and Predictive Key Biomarkers for Urinary Bladder Cancer

“…In the same study, it was also stated that it may be used as an individual effective diagnostic and prognostic biomarker for BCa, along with five other collagen family members. In our study, COL6A1 levels were found to be significantly downregulated in the blood plasma and urinary bladder tissue among BCa patients, substantiating previous findings in the literature [ 170 ]. In the latter study, it was suggested that COL6A1 and COL6A2 may act as standard collagens by constructing a physical barrier to inhibit BCa tumor growth and invasion.…”

Collagen Biomarkers Quantify Fibroblast Activity In Vitro and Predict Survival in Patients with Pancreatic Ductal Adenocarcinoma

“…Two collagens might have their own unique function, which is supported by the fact that specific chains of collagens can have differential functions. As opposed to the α3 chain of type VI collagen, which is pro-tumorigenic, the α1 and α2 chain of type VI collagen have shown to repress proliferation, migration, and invasion in a bladder cancer cell line [73]. Furthermore, recently Martino et al showed that the α1 and α2 chain of type VI collagen is highly expressed around dormant tumors compared to more aggressive tumors [74].…”

Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma

“…Collagen is one of the essential components which participate in the formation of focal adhesion [52]. Suppression of collagen might breach focal adhesion and dramatically enhance the invasion of tumor cells [53,54]. Therefore, we speculate that decreased collagen in GHPA may interfere with the formation of focal adhesion, leading to potential invasion of tumor.…”