Correlation of tissue plasminogen regulators expressed by esophageal adenocarcinoma with VEGF family members.

Abstract

37 Background: Esophageal cancer is known for its high potential of early lymphogenous metastases. The biological activity of plasminogen (PG) regulators, VEGFs and their receptors controls the growth and differentiation of cells, including malignant ones, the stability of the extracellular matrix, as well as processes of destruction of membranes and extracellular matrix, invasion of malignant cells, angio- and lymphangiogenesis. Our purpose was to study the role of PG regulators in the activation of VEGFs and their receptors in esophageal adenocarcinoma (EA) and its perifocal zone (PZ). Methods: Levels of uPA-Ag, uPA-act; tPA-Ag, tPA-act; PAI-1-Ag and PAI-1-act, VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were determined by ELISA in surgical specimens of EA (n = 28, st II, G2, T2-3N0-1M0). Statistical analysis was performed using Microsoft Office Excel 2010. Results: Levels of all proteins, except tPA, were higher in tumor (T) tissues than in the resection line (RL, p < 0.01). Protein levels, except uPA-Ag and tPA, in PZ were between levels in T and RL (p < 0.01); uPA-Ag, tPA-Ag and tPA-act were decreased in T and PZ compared with RL (p < 0.01); PAI-1-Ag in T and PZ was higher than in RL by 9.4 and 6.3 times, and PAI-1-act – by 10.7 and 1.9 times. Levels of VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were increased in T (p < 0.001), and in PZ they were between levels in T and RL (p < 0.001). Strong correlations were registered in EA T between uPA and VEGF-А (r = 86), uPA and VEGF-R1 (r = 81), uPA and VEGF-С (r = 79), uPA and VEGF-R3 (r = 76). A strong correlation between uPA and PAI-1 in T (r = 88) did not exclude PAI-1 biological effects in EA T and its PZ. PZ showed strong correlations between uPA and PAI-1 (r = 87), uPA and VEGF-А (r = 84), uPA and VEGF-С (r = 78). Conclusions: The strong correlations between the activation of uPA, PAI-1, VEGF-А, VEGF-С and their receptors in EA indicate interactions between them, realized both directly and through plasmin. The expression of the studied proteins in T and its PZ, compared to RL, demonstrates the effect of T on the content and activity of uPA, PAI-1, VEGF-A, VEGF-C and their receptors, with the following realization of biological properties that promote the progression of EA.