Positive association of collagen type I with non-muscle invasive bladder cancer progression

Abstract

PURPOSENon-muscle invasive bladder cancers (NMIBC) are generally curable, while ~15% progresses into muscle-invasive cancer with poor prognosis. While efforts have been made to identify genetic alternations associated with progression, the extracellular matrix (ECM) microenvironment remains largely unexplored. Type I collagen is a major component of the bladder ECM, and can be altered during cancer progression. We set out to explore the association of type I collagen with NMIBC progression.EXPERIMENTAL DESIGNThe associations of COL1A1 and COL1A2 mRNA levels with progression were evaluated in a multi-center cohort of 189 patients with NMIBCs. Type I collagen protein expression and structure were evaluated in an independent single-center cohort of 80 patients with NMIBCs. Immunohistochemical analysis was performed and state-of-the-art multi-photon microscopy was used to evaluate collagen structure via second harmonic generation imaging. Progression to muscle invasion was the primary outcome. Kaplan-Meier method, Cox regression, and Wilcoxon rank-sum were used for statistical analysis.RESULTSThere is a significant association of high COL1A1 and COL1A2 mRNA expression in patients with poor progression-free survival (P=0.0037 and P=0.011, respectively) and overall survival (P=0.024 and P=0.012, respectively). Additionally, immunohistochemistry analysis of type I collagen protein deposition revealed a significant association with progression (P=0.0145); Second-harmonic generation imaging revealed a significant lower collagen fiber curvature ratio in patients with invasive progression (P = 0.0018).CONCLUSIONSAlterations in the ECM microenvironment, particularly type I collagen, likely contributes to bladder cancer progression. These findings will open avenues to future functional studies to investigate ECM-tumor interaction as a potential therapeutic intervention to treat NMIBCs.

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

“…Over the last few years, accumulated evidences have indicated that some collagens are differentially expressed in cancer. Collagen type I contributes to pancreatic, lung, bladder, liver and breast cancer progression [7][8][9][10][11]. Collagen type IV (Col IV) levels are elevated in patients with colorectal liver metastases [12,13].…”

Study on collagen parameters in vulvar cancer and preneoplastic lesions by Second Harmonic Generation microscopy

“…Similarly, patients with parameters associated with more aggressive disease, considered a rare cancer of elderly women, has been increasing in incidence in younger women over the last few decades [16][17][18] . Studies on breast, head and neck, esophageal, and colorectal cancer using SHG reported that longer and denser COL in the tumor microenvironment was associated with tumor invasion 9,10 . Others have shown that the presence of tumor invasion was associated with higher COL quantity and uniformity, but lower organization 19,20 .…”

“…Over the last few years, studies on cancer development have focused on the role of remodeling of the extracellular matrix (ECM), more specifically on collagen fibers (COL), to tumor progression. COL are major components of the ECM and are important for the maintenance of tissue and organ structure and integrity 9,10 . However, its role surpasses the structural aspect, and it is considered to influence tumor invasiveness and metastasizing 9,10 .…”

Inducing intravesical hyperthermia of the ex-vivo porcine bladder wall: radiofrequency-induction versus recirculation using a custom-made device

“…With RF-HT, an effective mild hyperthermic temperature in the detrusor layer of the bladder neck and side wall could be more easily reached in most of the bladders, compared with C-HT with an inflow temperature of 46 C. Achieving effective hyperthermic temperatures at these depths may be beneficial for NMIBC patients if any residual tumor after TURBT is present (implying incomplete TURBT). Additionally, an increased amount of collagen in papillary tumor or sub-epithelial stroma is associated with progression to muscle invasion, which might be better heated by RF-HT [17]. In treatment of minimally muscle-invasive disease, HT at the detrusor level might be of value in experimental bladder-sparing therapy, for example with thermosensitive nanoparticles [18,19].…”