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

采用酶联免疫吸附法测定了129例非小细胞肺癌（NSCLC）标本提取物中免疫反应性肝细胞生长因子/散射因子（HGF/SF）的含量。扩散型BAC组织提取物的免疫反应性HGF/SF平均浓度（265.0±110.2 ng/100 mg蛋白）比孤立型BAC（13.9±15.9，P<0.005）、非BAC腺癌（13.8±14.9，P<0.001）、鳞状细胞癌（13.2±14.4，P<0.001）和大细胞癌（11.2±6.5，P<0.005）高19倍以上。HGF/SF免疫组化染色显示，弥漫性BAC肿瘤细胞中均可见高强度的HGF/SF染色，而孤立型BAC细胞中不可见高强度的HGF/SF染色。已知孤立性和弥漫性BAC具有不同的预后；后者比前者穷得多。我们的结果至少可以部分解释这种预后差异。接下来，采用酶联免疫吸附法（ELISA）测定了139例原发性人肺癌肿瘤提取物中PD-ECGF/TP的浓度。139个标本中的137个提取液中检测到PD-ECGF/TP，浓度范围为2.0 ~ 169.5单位/毫克蛋白质。腺癌（n=73）和鳞状细胞癌（n=49）患者的PD-ECGF/TP平均（±SD）浓度分别为30.7±22.9（范围，7.6 -169.5）和32.0±19.8（范围，8.0-84.4）单位/mg蛋白。小细胞肺癌组织提取物中PD-ECGF/TP的平均浓度（n=17, 3.65±2.01单位/毫克蛋白，范围，未检测到- 6.1）比腺癌（P= 0.005）或鳞状细胞癌（P< 0.00001）低8倍以上。小细胞肺癌和非小细胞肺癌之间PD-ECGF浓度的显著差异表明，这两种类型的肺癌使用了不同的血管生成途径。

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.