The circulating urokinase plasminogen activator (uPA) and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (NSCLC).
It has been suggested that uPA in cancer cells is up regulated by the p 185 kD form of the HER-2/neu oncogene. We elected to see if the extra cellular domain of HER-2/neu, the p 105 fraction, which is found in the circulation, has any regulatory influence on uPA or uPAR in those patients with NSCLC Levels of uPA, uPAR and p 105 HER-2/neu were determined in blood from age-matched controls and patients with advanced NSCLC. In the patients with NSCLC, samples were obtained before and following treatment. A large increase in both uPA and uPAR compared to controls was seen in the patients prior to treatment. The uPAR level post-treatment decreased from pre-treatment values, which is favorable. There was a significant increase in uPA and a decrease in HER-2/neu in the post-treatment time frame. Additionally, correlation analysis of circulating uPAR, uPA and HER-2/neu against each other in both the controls and treatment groups indicated no relationship. It appears that circulating uPA and uPAR are elevated in NSCLC patients. The up-regulation of uPA by HER-2/neu seen in lung cancer cells in vitro is apparently lost in the blood in vivo as is evidenced by the lack of correlation between them which is also true for the receptor as well.
Jumper
Cynthia
C
Department of Medicine, Texas Tech HSC and Southwest Cancer Center, Lubbock 79430, USA.
Cobos
Everardo
E
Lox
Charles
C
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D012016:Reference Values; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
C000715470:MAS1 protein, human; C524898:PLAUR protein, human; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator