Differences in plasminogen activation in primary rectal adenocarcinoma with and without liver metastasis.

Abstract

e15111 Background: Plasminogen activators play a key role in the cascade fibrinolytic system as they catalyze plasmin formation from plasminogen (PG). Plasminogen activators together with plasmin are directly or indirectly involved in tumor growth. The purpose of the study was to compare the plasminogen activation system in primary adenocarcinomas (РА) of the rectum (R) with and without liver metastases (LM). Methods: Tissues of tumors (РА, st. III, G2, 38-74 years) and their perifocal zone (PZ) with LM (T2-3NхM1, n = 24) and without them (T2-3N0M0, n = 32) were studied by ELISA. Results: The studied parameters did not differ in apparently intact R tissues in the resection line (RL) with and without LM. Plasmin-α2-antiplasmin complex (PAP) was 1.4 times higher in PA with LM than without LM (p < 0.05). Prourokinase and urokinase levels (uPA-Ag and uPA-act) were 12.4 and 3.7 higher than in RL. uPA-Ag and uPA-act in PA+LM were higher than without LM by 1.4 and 1.6 times. PG levels and α2-macroglobulin (α2M) activity in PA+LM were lower by 1.5 and 2.7 times than in PA without LM and lower than in RL (p < 0.01). All studied parameters, except α2M, in PA+LM were activated more than in PA without LM. Low α2M content supposed realization of effects of uPA and plasmin in insufficient inhibitory control. Most parameters in PZ+LM were between the levels in PA and RL being significantly different from both and significantly exceeding the values in PZ of PA without LM. α2М was an exception being 1.8 times lower in PZ of PA+LM than in PZ of PA without LM. The results demonstrated higher uPA and РАР levels in PA and its PZ with LM than without them, with increased PG consumption and decreased α2M activity in these parts of the rectum. Activation of plasminogen system in tissues of PA+LM and in PA without LM was unidirectional. Conclusions: Levels of uPA and PAP, as well as low α2M content in PA and PZ with LM can be used as an indicator of tumor metastatic activity.