Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Background: Earlier invitro studies have observed that loss of E-cadherin is responsible for progression and metastasis of cancer by upregulation of c-Jun protein. There being lack of simultaneous evaluation of matrix metalloproteinase (MMP) -2 and -9, E-cadherin and c-Jun mRNA and protein. Objective: This study aimed to correlate the above-mentioned parameters to evaluate the pathway of oral carcinogenesis. Methods: The study included 100 controls, 50 patients with oral precancerous conditions (OPC) and 100 oral cancer patients. MMPs were evaluated by gelatin zymography, ECAD and CJUN mRNA and protein expression by semi quantitative RT-PCR and western blot respectively. Results: The levels of active and total MMP-2 and MMP-9 were significantly higher in patients with OPC and oral cancer patients as compared to controls. A significant increase in truncated E-cadherin and c-Jun protein was observed in malignant tissues as compared to adjacent normal tissues while CJUN mRNA levels were comparable. Higher values of c-Jun protein and MMPs, and lower values of ECAD mRNA were associated with reduced overall survival. A positive correlation was observed between truncated E-cadherin, MMPs and c-Jun protein. Conclusions: MMPs modulate cell-cell adhesion by increasing truncation of E-cadherin resulting in loss of E-cadherin which is responsible for upregulation of c-Jun protein in oral cancer.

Glycoprotein electrophoretic patterns have potential to monitor changes associated with neoplastic transformation in oral cancer

Alterations in glycoproteins, important cell surface constituents, have long been associated with various malignancies. The present investigation therefore explored the clinical significance of a glycoproteomics approach in patients with oral precancerous conditions (OPC) and patients with oral cancer. The study included 80 oral cancer patients, 50 patients with OPC, and 84 controls. Native polyacrylamide gel electrophoresis followed by Schiff's staining was carried out to study the alterations in glycoproteins. The results showed significant elevation (p<0.0001) of 192 kDa, 170 kDa, 116 kDa and 44 kDa glycoproteins in oral cancer patients and patients with OPC compared with controls. The odds ratio indicated a significantly higher risk for oral cancer among users and especially chewers of tobacco. The levels of all the glycoprotein bands (192 kDa, 170 kDa, 116 kDa and 44 kDa) were higher in patients with a habit of tobacco use (WHT) than in patients with no habit of tobacco (NHT) and were also higher in WHT controls than in NHT controls. Moreover, a 230 kDa glycoprotein consistently appeared only in individuals with tobacco habits and an increasing trend was observed from WHT controls to patients with OPC to WHT oral cancer patients. In conclusion, the results indicated the potential utility of glycoprotein alterations in monitoring sequential changes occurring due to tobacco consumption during neoplastic transformation.