Role of Prostaglandin E1 and Copper in Angiogenesis

The interstitial fluid of MTW9A and Walker carcinomas and their ethanol extract induced strong angiogenic response in the rabbit (New Zealand White) corneal test. The fluid collected in vivo was rich in E-type prostaglandins, and prostaglandin E1 (PGE1) in particular was strongly angiogenic at the l...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1982-08, Vol.69 (2), p.475-482
Main Authors: Ziche, Marina, Jones, John, Gullino, Pietro M.
Format: Article
Language:English
Subjects:
Alprostadil
Animals
Carcinoma 256, Walker - metabolism
Ceruloplasmin - pharmacology
Copper - analysis
Copper - pharmacology
Copper - physiology
Cornea - analysis
Cornea - blood supply
Dinoprost
Dinoprostone
Epoprostenol - pharmacology
Female
Indomethacin - administration & dosage
Male
Mice
Mice, Inbred BALB C
Neoplasms, Experimental - metabolism
Neovascularization, Pathologic - drug effects
Prostaglandins E - pharmacology
Prostaglandins E - physiology
Prostaglandins F - pharmacology
Rabbits
Rats
Rats, Inbred Strains
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Summary:The interstitial fluid of MTW9A and Walker carcinomas and their ethanol extract induced strong angiogenic response in the rabbit (New Zealand White) corneal test. The fluid collected in vivo was rich in E-type prostaglandins, and prostaglandin E1 (PGE1) in particular was strongly angiogenic at the lowest dose as compared with the angiogenic responses of prostaglandins E2, I2, and F2α. Neoplastic fibroblasts also induced a strong angiogenic response, but in indomethacin-treated rabbits neovascularization failed to occur. Copper was concentrated in the cornea during PGE1-induced neovascularization, and copper-deficient rabbits were unable to mount an angiogenic response in the corneal test. Ceruloplasmin, the copper carrier of plasma, was found to be angiogenic at high doses. In indomethacin-treated rabbits, however, ceruloplasmin at the same high doses failed to induce angiogenesis. The experiments are interpreted to indicate that angiogenesis is the end result of a sequence of events, two of which are PGE1 production and copper mobilization in the tissue where neovascularization occurs.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/69.2.475