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

Abstract

Detectable levels (≥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 9α,11β-prostaglandin F₂, prostaglandin F_2α, prostaglandin D₂, prostaglandin E₂, thromboxane B₂ and 6-keto-prostaglandin F_1α 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 ≥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), bronchioloalveolar cell carcinoma (2 of 2 cell lines) and small cell carcinoma (0 of 9 cell lines). Three different prostanoid species accumulated to mean levels ≥2 pmol/10⁶ cells. Prostaglandin E₂ levels exceeded 2 pmol/10⁶ cells in 14 of the 16 cell lines in which this prostanoid accumulated to detectable levels. Cumulative levels of prostaglandin F_2α exceeded 2 pmol/10⁶ cells in 9 of the 15 cell lines in which prostaglandin F_2α 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. 9α,11β-prostaglandin F₂ and 6-keto-prostaglandin F_1α accumulated to detectable levels in the culture medium of one cell line, while prostaglandin D₂ accumulation to detectable levels was observed in two cell lines. Stimulation of cultured human lung tumor cells exhibiting PGH synthase activity ≥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.