Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer.
The permeation of macromolecular FITC-labeled dextran (molecular weight 70,000) through bovine aortic endothelial cells (BAEC) monolayer, which were cultured for 5 days with conditioned medium prepared from mouse melanoma B16, was increased. However, when BAEC, which were cultured with normal medium until confluent, were treated with B16 conditioned medium (B16-CM) for 30 min, the permeability did not increase. The B16-CM also increased the permeability of the endothelial monolayers of bovine veins and the human umbilical vein, but did not increase that of the epithelial monolayer. The B16-CM did not alter the distribution or content of F-actin on the BAEC. BAEC cultured in the presence of B16-CM for 5 days were detached from the dish, and then seeded into a chamber at one-fifth of confluent cell density. After 5 days of culture in normal medium, the BAEC were grown to confluence and their permeability was increased. These findings suggest that B16-CM increased the endothelial permeability irreversibly without the decrease of F-actin, and that soluble factor(s) which were secreted from the tumor cells participate in the construction of the hyperpermeable structure of tumor vessels in vivo.
Utoguchi
N
N
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Mizuguchi
H
H
Saeki
K
K
Ikeda
K
K
Tsutsumi
Y
Y
Nakagawa
S
S
Mayumi
T
T
D000199:Actins / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D046911:Macromolecular Substances; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051381:Rats; D014407:Tumor Cells, Cultured
D000199:Actins; D017077:Culture Media, Conditioned; D046911:Macromolecular Substances