Bladder cancer is the 2nd most common urologic malignancy amongst the males after prostate cancer. Migration is one of the important processes fundamental to cell invasion and dissemination. Role of extracellular matrix (ECM) proteins is also very important in this crucial process and cannot be ignored. ECM proteins are involved in cell migration, tissue remodeling, angiogenesis and cell adhesion.
Fibulin-1 is cysteine-rich, calcium-binding extracellular matrix and plasma protein that has been implicated as playing a role in tumour progression by modulating cell morphology, growth, adhesion, and motility. Increased plasminogen activator (PA) secretion has been observed in malignant cells and tissue and PA is thought to be involved in the processes of tumorigenesis, cancer invasion and metastasis. Laminins are also important for proliferation, differentiation, growth, migration & angiogenesis. Besides the structural function of nidogens, it has long been suggested that nidogens play a role in cell attachment and tumor angiogenesis.
This study was aimed to investigate the expression and significance of ECM proteins (Fibulin-1, uPA, Laminin and Nidogen) in Urothelial carcinoma of bladder.
Material & Methods
The study cohort consisted of 90 subjects; 45 patients with Urothelial carcinoma of bladder (High grade Muscle Invasive MI (T2): 14, High grade Non-Muscle Invasive NMI (T1): 12, Low grade LG: 19; According to the WHO/ISUP 2004 classification and T staging) and 45 healthy controls. Circulatory levels of Fibulin-1, Laminin and Nidogen were measured using high sensitivity ELISA kits. uPA activity was measured by activity assay kit. The mRNA expressions of these molecules in the Peripheral blood mononuclear cells (PBMC) were further analyzed by Real Time RT-PCR. The data was analyzed statistically and correlated with the severity of the disease.
Statistical significant (p < 0.001) increase was observed in Fibulin-1, Nidogen, uPA and Laminin levels as compared to controls and found to be significantly correlated with each other. Increased mRNA expression for all these molecules has also been observed in the isolated PBMC by qRT-PCR.
The elevated serum/plasma levels and increased quantitative expression of these ECM proteins suggests their involvement in the pathogenesis of the disease. This study suggests that rise in ECM proteins might contribute to the complicated and unregulated process of metastasis in Urothelial carcinoma of bladder. The association of extracellular matrix proteins and the prognosis of the disease may lead to have a better approach in treating the bladder cancer patients with a combination therapy.