Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases.
To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The immunostaining scores of the prostaglandin biosynthetic pathway markers were significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition, there were significant correlations between two markers of the prostaglandin biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean immunostaining scores for the prostaglandin biosynthetic pathway markers were significantly higher for cases with high count groups than low count groups for MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic pathway markers may act synergistically and enhance tumor angiogenesis, the expression of angiogenic factors, and metastases in patients with NSCLC.
Yoshimoto
Akihiro
A
Department of Hematology-Oncology, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan. yoshimoto@med3.m.kanazawa-u.ac.jp
Kasahara
Kazuo
K
Kawashima
Atsuhiro
A
Fujimura
Masaki
M
Nakao
Shinji
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D054834:Lipocalins; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D008297:Male; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D015398:Signal Transduction; D013930:Thromboxane-A Synthase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D054834:Lipocalins; D008565:Membrane Proteins; D011453:Prostaglandins; D042461:Vascular Endothelial Growth Factor A; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases; D013930:Thromboxane-A Synthase