Is there a role of platelet-activating factor in human lung cancer?
Platelet-activating factor (PAF) is a lipid mediator that stimulates the in vitro growth of various human tumour cell lines and that enhances the effect of vascular endothelial growth factor that plays a key role during angiogenesis of human cancer. In this study, we assessed the levels of PAF and of the acetylhydrolase activity (AHA, the PAF degrading enzyme) in patients with lung cancer. Results indicated no significant differences between blood PAF amounts of lung cancer patients (91+/-33 pg/ml, n=31) and a control group of patients with chronic obstructive pulmonary disease (COPD) induced by habitual smoking (117+/-28 pg/ml, n=10). Similarly, their serum AHA levels were not different (67.9+/-3.0 nmol/min/ml as compared to 68.3+/-5.2 nmol/min/ml for lung cancer patients and controls, respectively). In contrast, PAF amounts were markedly (P=0.01, t-test for paired data) reduced in the lung tumour tissues (77+/-29 pg/g, n=10) as compared to the non-tumour tissues (208+/-67 pg/g, n=10). These low levels of PAF were not related to a lower amounts of the lyso-PAF precursor but to an elevated (P=0.01, t-test for paired data) AHA in the tumour tissues (37.0+/-4.9 nmol/min/g, n=10) as compared to the non-tumour tissues (24.6+/-2.6 nmol/min/ml, n=10). Reverse transcriptase polymerase chain reaction experiments showed the presence of the PAF receptor (PAF-R) transcript 1 but not transcript 2 in blood mononuclear cells of lung cancer patients and COPD patients. Flow cytometry experiments did not highlight differences in the number and the distribution of PAF-R on their circulating leukocytes. In conclusion, this clinical study highlights no evidence for a potential important role of PAF during human lung cancer.
Denizot
Y
Y
UMR CNRS 6101, Laboratoire d'immunologie, Faculté de Médecine, 2 rue Dr Marcland, 87025 Limoges, France. yves.denizot@unilim.fr
Desplat
V
V
Drouet
M
M
Bertin
F
F
Melloni
B
B
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D017931:DNA Primers; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase