VPB0736 - Prothrombin can modulate its expression in colon cancer cells

Background: Prothrombotic disorders are the main comorbidity of cancer and can significantly contribute to its morbidity and mortality. Thrombin, pivotal regulator of the coagulation cascade, influences cancer growth and invasion through the activation of protease-activated receptors (PARs). Prothrombin, precursor of thrombin, is predominantly synthesized in the liver and secreted into the bloodstream, but it can also be expressed in the cancer cells. Recent data show that prothrombin binds to the transmembrane receptors, which activate migration and invasion and which are up-regulated in cancers. Even though there is a vast amount of evidence for the effects of thrombin in cancer progression, there are little data of its activation and effects of its precursor - prothrombin, on cancer cells.

Aims: Evaluate the effects of exogenous prothrombin treatment on the prothrombin expression in cancer cell lines.

Methods: Permanent colon cancer cell lines (Caco2, SW480, SW620, HT29 and HCT116) were treated with commercial human prothrombin. Real-Time PCR (qPCR) for relative quantification of prothrombin mRNA expression was performed by TaqMan Gene Expression Assays using cDNA from cell lines as a template. Expression pattern was analyzed 24h after the treatment. Data were compared with results of untreated cell lines.

Results: This study confirms that analyzed colon cancer cell lines express prothrombin. The detected effect of the treatment with exogenous prothrombin differed between cell lines. There was significantly lower level of prothrombin expression in treated Caco2, SW620 and HCT116 cell lines in comparison to untreated.

Conclusion(s): Our results indicate that prothrombin (originated from circulation or expressed by cancer cell), although inactive form, can regulate its expression in colon cancer cells.