A possible role of TGF-beta in the formation of malignant effusions.
The detailed mechanisms underlying the formation of malignant effusions are incompletely defined. In order to determine whether transforming growth factor-beta (TGF-beta) would contribute to the formation of malignant effusions, we investigated the effect of TGF-beta on the morphology, growth, and permeability of human mesothelial cells, which are thought to serve as a permeability barrier in the pleuroperitoneal cavities. 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 in the cells. Each cell increased in size as did the volume of the intercellular spaces. TGF-beta also significantly inhibited the growth of mesothelial cells at a concentration ranging from 0.1 to 10 ng/ml. This 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 monolayer as assessed by a FITC-albumin permeability assay. In our clinical analysis using 10 effusion samples obtained from patients with various 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 that TGF-beta plays an important role in the formation of malignant effusions through structural and functional damage to the mesothelial cells. Malignant effusions may accumulate in the pleuroperitoneal cavity as a result of the mesothelial cell damage caused by this cytokine which is released from disseminated cancer cells.
Ikubo
A
A
First Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Morisaki
T
T
Katano
M
M
Kitsuki
H
H
Anan
K
K
Uchiyama
A
A
Tanaka
M
M
Torisu
M
M
D000328:Adult; D000368:Aged; D001201:Ascites / Q000473:pathology*; D002455:Cell Division; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009852:Omentum; D016066:Pleural Effusion, Malignant / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D006131:Growth Inhibitors; D016212:Transforming Growth Factor beta