A POSSIBLE ROLE OF TGF-BETA IN THE FORMATION OF MALIGNANT EFFUSIONS

The detailed mechanisms underlying the formation of malignant effusion s are incompletely defined. In order to determine whether transforming growth factor-beta (TGF-beta) would contribute to the formation of ma lignant effusions, we investigated the effect of TGF-beta on the morph ology, growth, and permeability of human mesothelial cells, which are thought to serve as a permeability barrier in the pleuroperitoneal cav ities. Treatment of the mesothelial cells with a TGF-beta dose ranging from 0.1 to 10 ng/ml for 96 hr induced distinct morphologic changes i n the cells. Each cell increased in size as did the volume of the inte rcellular spaces. TGF-beta also significantly inhibited the growth of mesothelial cells at a concentration ranging from 0.1 to 10 ng/ml. Thi s growth inhibition was blocked completely by the addition of anti-TGF -beta antibody. Treatment of the mesothelial cells with 2.0 ng/ml TGF- beta significantly increased the permeability of a mesothelial cell mo nolayer as assessed by a FITC-albumin permeability assay. In our clini cal analysis using 10 effusion samples obtained from patients with var ious types of carcinoma cells, considerable level of TGF-beta could be detected by ELISA, ranged from 0.90 to 8.75 ng/ml. Our data suggest t hat TGF-beta plays an important role in the formation of malignant eff usions through structural and functional damage to the mesothelial cel ls. Malignant effusions may accumulate in the pleuroperitoneal cavity as a result of the mesothelial cell damage caused by this cytokine whi ch is released from disseminated cancer cells. (C) 1995 Academic Press , Inc.