Profiles of Prostaglandin Biosynthesis in Normal Lung and Tumor Tissue from Lung Cancer Patients

Abstract

Prostaglandin (PG) biosynthetic profiles from endogenous arachidonic acid were determined by capillary gas chromatography-mass spectrometry in matched fresh normal lung (NL) and lung cancer (LC) tissue fragments obtained from 42 individual LC patients at the time of diagnostic thoracotomy. The histological diagnoses represented were squamous cell carcinoma (N = 20), adenocarcinoma (N = 7), small cell carcinoma (N = 4), mixed cell carcinoma (N = 2), bronchioloalveolar cell carcinoma (N = 2), large cell undifferentiated carcinoma (N = 3), bronchial carcinoid (N = 1), and metastatic tumors (N = 3). When PG biosynthesis was determined in NL tissue separately, low mean levels of PGE₂ and PGF_2α (<2 pmol/mg protein/15 min), intermediate levels of PGD₂ and 6-keto-PGF_1α (6KPGF_1α) (2–7 pmol/mg protein/15 min), and high levels of thromboxane B₂ (TXB₂) (>7 pmol/mg protein/15 min) were observed. There was no particular correlation with cigarette smoking history and PG biosynthesis in NL. When PG production in LC tissue was evaluated separately, high levels of PGE₂, PGF_2α, and 6KPGF_1α as well as TXB₂ and low levels of PGD₂ were noted. In addition, LC tissue from cigarette smokers demonstrated elevated levels of PGE₂, 6KPGF_1α, and TXB₂ when compared to current nonsmokers with LC (P < 0.05 in all instances). Simultaneous comparison of PG production in matched LC and NL tissue from individual patients indicated increased biosynthesis of PGE₂ and PGF_2α and low levels of PGD₂ in LC compared to NL tissue (P < 0.05 in all instances; paired, two-tailed, Student's t test). Individual comparison of PG biosynthesis according to LC histological cell type revealed that PGE₂ and PGF_2α were consistently elevated in all four common primary LC histological cell types, the only exception being large cell undifferentiated carcinoma. Interestingly, this latter LC histological cell type presented a unique profile with lower levels of PGE₂ and PGD₂ in LC than in NL tissue (P < 0.05 in both instances). In addition, the biosynthesis of all 5 PGs studied was consistently higher in primary than metastatic adenocarcinomas of the lung (P < 0.05 in all instances). No differences were observed in NL and LC tissue for the major LC histological cell types when PGD₂, TXB₂, or 6KPGF_1α biosyntheses were compared. These findings indicate that the profiles of PG biosynthesis in LC and NL tissue from individual patients may differ substantially. These differences may reflect, in part, contributions to the PG biosynthetic profile unique to malignant cells.