Active metabolism of arachidonic acid by Kaposi sarcoma cells cultured from lung biopsies (KS-3); identification by HPLC and MS/MS of the predominant metabolite secreted as the 11,12-epoxy-eicosatrienoic acid.
The development of long-term culture of AIDS-KS cells has allowed us to investigate further a possible vascular origin of Kaposi sarcoma. Taking into account the relative specificity of arachidonic acid (AA) metabolism according to cell type, the AA 'cascade' was analyzed in cultured KS-3 cells established from lung biopsies and compared to human umbilical venous endothelial (H-UVE) cells and human myometrial smooth muscle (H-MSM) cells, under basal conditions and after stimulation with vasoactive agents such as histamine or thrombin. Considering strictly the 'prostaglandin' profile given by RIAs, the metabolism of AA was closer, whilst not identical, to H-UVE than to H-MSM cells. However, evaluation of all the eicosanoids released from [3H]AA labeled KS-3 cells revealed that the predominant metabolite was not prostacyclin (PGI2), as suggested from PG RIAs, but an epoxy-eicosatrienoic acid (EET), identified as the 11, 12 isomer by HPLC and MS/MS. The synthesis of this EET is probably cytochrome P-450 monooxygenase dependent. Its potential role in the development of the KS tumor cells is under investigation.
Dray
F
F
U207 INSERM, URIA Institut Pasteur, Paris, France.
Vulliez-Le Normand
B
B
Deroussent
A
A
Briquet
I
I
Gabellec
M M
MM
Nakamura
S
S
Wahl
L M
LM
Gouyette
A
A
Salahuddin
Z S
ZS
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001706:Biopsy; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D011863:Radioimmunoassay; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013917:Thrombin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016718:Arachidonic Acid; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D006632:Histamine; D013917:Thrombin; D015126:8,11,14-Eicosatrienoic Acid