Objective: 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.
Methods: 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.
Results: 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).
Conclusions: 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.