Blood coagulation proteins in cancer: increased expression of Tissue Factor and PAR-1 in esophageal cancer Ribeiro, F.S.1; Simão, T.A.1; Ribeiro-Pinto, L.F.1; Albano, R.M.1 and Monteiro, R.Q.2
1Departamento de Bioquímica, IBRAG, UERJ; 2Instituto de Bioquímica Médica, UFRJ, Rio de Janeiro, Brazil - email: robsonqm@bioqmed.ufrj.br
A correlation between cancer and blood procoagulant states has been well documented. Tissue factor (TF) is a transmembrane 46-kDa protein that initiates blood coagulation when bound to factor VIIa (FVIIa). Aberrant TF expression in tumor cells contributes to the prothrombotic state in cancer patients. However, recent studies indicate that TF participate in tumor growth, metastasis and angiogenesis through a pathway that is independent of blood coagulation. Also, a family of G protein-coupled receptors known as protease-activated receptors (PARs) has been implicated in tumor biology. These receptors may be activated by blood coagulation proteases including thrombin, FVIIa and FXa. In this study we compared the expression of TF, PAR-1 and PAR-2 between normal and tumor tissue samples obtained from patients with esophageal cancer. Tissue samples were obtained from 16 patients submitted to esophagectomy or endoscopy at HUPE-UERJ (Rio de Janeiro, Brazil) or at Gastrocentro, Hospital das Clínicas, UNICAMP (Campinas, Brazil). Tumor samples and the corresponding normal mucosae were obtained and the diagnosis was confirmed by histopathological analysis of adjacent tissues. Total RNA was extracted and further analyzed by reverse transcriptase (RT)-PCR. Our results showed that expression of mRNA for TF and PAR-1 was significantly higher in tumor samples. On the other hand, the levels of mRNA expression for PAR-2 were statistically similar in normal and tumor samples. Previous studies demonstrated that PAR-mediated cell signalling is involved in interleukin-8 (IL-8) expression by a variety of cells. We further analyzed the IL-8 expression in tumor and normal samples. RT-PCR showed an increased expression of mRNA for IL-8 in tumor samples. Our data indicate that TF and PAR-1 might play an important role in esophageal cancer.
Supported by FAPERJ, CNPq, FECB, FAF, FUJB and CAPES.
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