EVIDENCE FOR PROSTANOID BIOSYNTHESIS AS A BIOCHEMICAL FEATURE OF CERTAIN SUBCLASSES OF NON-SMALL CELL CARCINOMAS OF THE LUNG AS DETERMINED IN ESTABLISHED CELL-LINES DERIVED FROM HUMAN-LUNG TUMORS

  • 15 February 1989
    • journal article
    • research article
    • Vol. 49  (4) , 826-832
Abstract
Detectable levels (.gtoreq. 0.2 pmol/106 cells) of one or more prostanoid species resultant to calcium ionophore A23187-induced biosynthesis from endogenous arachidonic acid were distributed in 28 cell lines derived from different histological classes of lung tumors as follows: large cell undifferentiated carcinoma (3 of 3 cell lines); adenosquamous carcinoma (1 of 2 cell lines); squamous cell carcinoma (0 of 2 cell lines); adenocarcinoma (9 of 10 cell lines); bronchioloalveolar cell carcinoma (2 of 2 cell lines); and small cell carcinoma (1 of 9 cell lines). Using the mean levels of 9.alpha.,11.beta.-prostaglandin F2, prostaglandin F2.alpha., prostaglandin D2, prostaglandin E2, thromboxane B2 and 6-ketoprostaglandin F1.alpha. as an index of prostaglandin H (PGH) synthase activity, the distribution in cell lines representative of the different histological classes of human lung tumors exhibiting PGH synthase activity exceeding mean values .gtoreq. 2 pmol/106 cells was as follows: large cell undifferentiated carcinoma (3 of 3 cell lines), adenosquamous carcinoma (1 of 2 cell lines), adenocarcinoma (8 of 10 cell lines), bronchioalveolar cell carcinoma (2 of 2 cell lines) and small cell carcinoma (0 of 9 cell lines). Three different prostanoid species accumulated to mean leels .gtoreq. 2 pmol/106 cells. Prostaglandin E2 levels exceeded 2 pmol/106 cells in 14 of the 16 cell lines in which this prostandoid accumulated to detectable levels. Cumulative levels of prostaglandin F2.alpha. exceeded 2 pmol/106 cells in 9 of the 15 cell lines in which prostaglandin F2.alpha. reached detectable levels. Detectable levels of thromboxane B2 were observed in five cell lines with thromboxane B2 accumulation exceeding 2 pmol/106 cells in two of the five cell lines. 9.alpha.,11.beta.-prostaglandin F2 and 6-ketoprostaglandin F1.alpha. accumulated to detectable levels in the culture medium of one cell line, which prostaglandin D2 accumulation to detectable levels was observed in two cell lines. Stimulation of cultured human lung tumor cells exhibiting PGH synthase activity .gtoreq. 2 pmol/106 cells in the presence of 10-5 M exogenous arachidonic acid resulted in a 2- to 4-fold increase in the accumulation of individual prostanoids, while the inclusion of a 10-5 M exogenous concentration of arachidonic acid failed to stimulate detectable prostanoid production in human lung tumor cells in which PGH synthase activity was not previously expressed. The predominance of PGH synthase activity in cell lines derived from human non-small cell carcinomas of the lung suggest that prostanoid biosynthesis may be characteristic of tumor cells comprising certain histological subclasses of human non-small cell carcinomas of the lung, particularly adenocarcinoma, bronchioloalveolar cell carcinoma, large cell undifferentiated carcinoma, and possibly adenosquamous carcinoma.