Interleukin (IL)-6 as a pancreas carcinoma-derived vascular permeability regulator in vitro.
The interaction between pancreas adenocarcinoma and vascular endothelial cells in vitro was investigated. Culture media of pancreas carcinoma cells PCI-10, but not PCI-24, induced an augmented albumin permeability across the endothelial monolayer, an event which was blocked by the calmodulin antagonist, W-7. Only marginal inhibitory effects were obtained using protein kinase inhibitors, H-7 and HA-1004. When cytokine production by pancreas carcinoma cells was examined, production of IL-6 in large amounts by PCI-10, but not by PCI-24 cells was evident. As recombinant IL-6 generated a dose-dependent permeability increase, and as this effect was inhibited by W-7, we considered that the enhancement of vascular permeability was mediated by this cytokine. The activity of culture supernatants for enhanced permeability was almost completely absorbed by the addition of an antibody specific for IL-6. Tumor-derived IL-6 as a soluble mediator regulates vascular permeability in vitro, and the production of this factor by pancreas adenocarcinoma cells presumably modulates biologic behavior.
Omi
M
M
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ishikura
H
H
Ishizu
A
A
Takahashi
T
T
Kato
H
H
Yoshiki
T
T
D000230:Adenocarcinoma / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D002147:Calmodulin; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012709:Serum Albumin; D013449:Sulfonamides; C017967:W 7