Mechanism of Lung Cancer Spread: Role of Protease and Its Inhibitor

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Immunoreactive hepatocyte growth facto/scatter factor (HGF/SF) was measured in extracts prepared from 129 non-small cell lung cancer (NSCLC) specimens using an enzyme-linked immunosorbent assay. The mean concentration of immunoreactive HGF/SF was more than 19-fold higher in tissue extracts from diffuse-type BAC (265.0±110.2 ng/100 mg protein) than in those from solitary-type BAC (13.9 ±15.9, P<0.005), non-BAC adenocarcinoma (13.8±14.9, P<0.001), squamous cell carcinoma (13.2± 14.4, P<0.001), or large cell carcinoma(11.2 ± 6.5, P<0.005). Immnunohistochemical staining for HGF/SF revealed that intense HGF/SF staining was uniformly observed in diffuse-type BAC tumor cells, but not in solitary-type BAC. The solitary and diffuse forms of BAC are known to have different prognoses; the latter is much poorer than the former. Our results may at least partly explain this difference in prognosis. Next, the concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured using an enzyme-linked immunosorbent assay (ELISA). PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 units/mg protein. The mean (±SD) PD-ECGF/TP concentrations in patients with adenocarcinoma (n=73) and squamous cell carcinoma (n=49) were 30.7 ± 22.9 (range, 7.6 -169.5) and 32.0 ±19.8 (range, 8.0-84.4) units/mg protein, respectively. A more than 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small-cell lung carcinoma (n=17, 3.65±2.01 units/mg protein, range, not detected - 6.1) than in those from adenocarcinomas (P=.00005) or squamous cell carcinomas (P<.00001). The striking difference in PD-ECGF concentrations between small cell and non-small cell lung cancer suggests that alternative pathways for angiogenesis are used by these two types of lung cancer.