Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro.
Tumor specimens of non-small cell lung carcinomas (NSCLC) from previously untreated patients (n = 153) were analysed immunohistochemically for expression of vascular endothelial growth factor (VEGF), VEGF-receptor (Flt-1), basic fibroblast growth factor (bFGF) and FGF-receptor (FGFR-1, (Flg). Expression of the proteins was compared with the in vitro response of the tumors against doxorubicin. The data clearly demonstrate that a significant relationship exists between VEGF (p < 0.001) and Flt-1 expression (p < 0.01) and drug response. The expression of VEGF and Flt-1 was lower in resistant than in sensitive tumors. In contrast, no significant interrelationship was found between expression of bFGF and response to doxorubicin. However, there exists a significant correlation between the expression of FGF-receptor (FGFR-1) and the response of the carcinomas to doxorubicin (p < 0.05). Expression of FGFR-1 was more frequently negative or weak in resistant and more frequently moderate or high in sensitive NSCLC. The data from this investigation clearly demonstrate that a significant interrelationship exists between the expression of VEGF, VEGF-receptor Flt-1 and FGF-receptor, FGFR-1 and the response of NSCLC to doxorubicin in vitro.
Volm
M
M
German Cancer Research Center, Heidelberg, Germany.
Koomägi
R
R
Mattern
J
J
Stammler
G
G
D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000188:drug therapy; D004317:Doxorubicin / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D000091344:Filaggrin Proteins; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D008222:Lymphokines / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008222:Lymphokines; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D004317:Doxorubicin; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor