Interaction of α2-macroglobulin with kallikrein and plasmin in ascitic fluid in ovarian cancer.

Abstract

e17030 Background: The kallikrein (KLKs) family is considered to be a regulator of many systems of limited proteolysis but can also be involved into pathology. Plasmin (P) regulates functions and density of the extracellular matrix, angiogenesis, maturation of gametes, sanation of cavities, tissues and body fluids, development of inflammation and malignant tumors. α2-Macroglobulin (α2M) is a molecular component of the body's endogenous protection. Ascitic fluid (AF) in various diseases of the ovaries is the biological environment valuable for the study of the affected organism containing protein about 20-50 g/L. KLKs, their proenzymes (pro-KLKs), Р, plasminogen (PG) and α2М in AF are poorly studied. Our purpose was to analyze the proteinase-inhibitory balance in AF of patients with ovarian cystadenocarcinoma (CAC) and tuberculosis of the uterine appendages (TA) to reveal its role in the development of the diseases and targets for the therapy. Methods: KLKs, pro-KLKs, Р, PG and α2М in AF in CAC of one ovary (n=26, T3-4N0M0) were compared with the levels in AF of TA patients before treatment (n=11). All women were menopausal, aged 56.5±2.6 years. KLKs, pro-KLKs, Р, PG and α2М were determined before treatment using the U-2900 UV Solutions double-beam spectrophotometer (USA), the result was calculated per 1 mg of protein (by Lowry). The protein content in AF was comparable to the blood plasma one, so we took the values in the plasma of healthy donors as the norm (N). The data were processed using the Statistica 10 program. Results: The exudate is believed to occur mainly from inflammation-damaged vessels. High protein content in AF in CAC and TA allowed us to consider AF as the exudates. The pro-KLKs/KLKs ratio reflecting the rates of KLKs formation in AF was decreased in TA and CAC by 4.6 and 6.7 times compared to N. The РG/Р ratio in AF in CAC was decreased by 3.8 times; in TA it was similar to N with increased PG and P. The KLKs/α2М ratio in TA and CAC exceeded N by 4.6 and 2.7 times. The Р/α2М ratio in TA and CAC was 6.5 and 4.5 times higher than N. Conclusions: Activity of KLKs and P in AF in CAC and TA was higher than in the blood plasma of healthy donors. Activity of α2М in AF in CAC and TA was not sufficient to control KLKs and P.