Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors.
OBJECTIVE
Prostanoids are important mediators of pulmonary vaso- and bronchotone regulation and strongly influence inflammatory reactivity. The product of cyclooxygenase (Cox), prostaglandin H(2), is further metabolized via downstream enzymes into the different effective metabolites. The specific cellular equipment with certain downstream enzymes crucially determines the cellular reactivity by generation of functionally different prostanoid metabolites.


METHODS
To elucidate the role of arachidonic acid metabolism via the cyclooxygenase pathway in different human lung tumors, expression of cyclooxygenase isoenzymes (Cox-1 and Cox-2) and downstream enzymes of prostanoid metabolism was investigated in human non-small cell lung cancer and normal human lung tissue by immunohistochemical techniques.


RESULTS
In comparison to strong Cox-1 reactivity in airways and endothelial cells of normal lung specimens, only 4 of 15 adenocarcinomas showed infrequent Cox-1 expression. All lung cancer specimens displayed an increased Cox-2 immunostaining pattern with strong reactivity in adenocarcinomas and lower reactivity in squamous cell carcinomas. Adenocarcinomas and squamous cell carcinomas were also positive for thromboxane A(2) synthase, prostaglandin D(2) synthase, and prostaglandin E(2) synthase, but not for prostacyclin synthase. Endothelial cells of vessels found within or near the tumor show extensive immunostaining of Cox-2 and thromboxane A(2) synthase, whereas endothelial cells of normal lung specimens, in contrast, expressed Cox-1 and prostacyclin synthase.


CONCLUSIONS
We conclude that non-small cell lung cancer shows a specific Cox-/downstream-enzyme expression pattern, which is specifically altered in lung tumor cells and tumor supplying vessels in contrast to normal lung tissue. This may have major impact on tumor progression and tumor-associated inflammation via an altered prostanoid metabolism with consecutive tumor-associated blood flow distribution.
Ermert
Leander
L
Department of Pathology, Justus-Liebig-University Giessen, Germany. leander.ermert@anatomie.med.uni-giessen.de
Dierkes
Christian
C
Ermert
Monika
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000378:metabolism
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D003577:Cytochrome P-450 Enzyme System; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase