Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase Concentrations Differ in Small Cell and Non-small Cell Lung Cancer

Abstract

Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been implicated in cancer angiogenesis, which is critical for tumor growth and metastasis. We investigated the relationship between the tissue concentration of PD-ECGF/TP and the clinicopathologic status in human lung cancer. The concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured by using a highly specific and sensitive enzyme-linked immunosorbent assay. PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 U/mg protein. PD-ECGF/TP concentrations in patients with adenocarcinoma (n = 73) and squamous cell carcinoma (n = 49) were (mean +/- SD) 30.7+/-22.9 U/mg protein (range, 7.6 to 169.5 U/mg protein) and 32.0+/-19.8 U/mg protein (range, 8.0 to 84.4 U/mg protein), respectively. No significant difference was found in the PD-ECGF/TP concentration between these two types of non-small cell lung cancer (NSCLC). However, a > 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small cell lung cancer (SCLC) (n = 17; 3.65+/-2.01 U/mg protein, ranging from undetectable to 6.1 U/mg protein) than in those from adenocarcinomas (p = 0.00005) or squamous cell carcinomas (p < 0.00001). The striking difference in PD-ECGF/TP concentrations between SCLC and NSCLC suggests that these two types of lung cancer use alternative pathways for angiogenesis. The present study suggests that inhibitors of PD-ECGF/TP, which have been recently developed and are under laboratory investigation to test their effectiveness as treatments for various types of cancer, may not be effective against SCLC.