Morita S, Sato A, Hayakawa H, Ihara H, Urano T, Takada Y, Takada A
Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Int J Cancer. 1998 Oct 29;78(3):286-92. doi: 10.1002/(SICI)1097-0215(19981029)78:3<286::AID-IJC4>3.0.CO;2-R.
The transcriptional localizations of urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitors (PAI-1 and PAI-2), which are possibly involved in cancer metastasis, have not been determined in human lung cancer. To identify their regulation in primary non-small-cell lung cancer, we assayed mRNA levels by Northern blot analysis in 25 cases and determined the localizations of mRNA by in situ hybridization in 10 cases. The amounts of uPA and PAI-2 mRNA were significantly higher in cancerous relative to normal lung tissues. However, no significant difference was observed in uPAR and PAI-1 mRNA levels. All transcripts were present in cancer cells and were predominantly located in tumor edges in several cases. In addition, PAI-1 transcripts were more abundant in poorly and moderately differentiated carcinomas relative to well-differentiated carcinomas and PAI-2 transcripts were more abundant in squamous cell carcinomas than in adenocarcinomas. Thus, PAIs may be involved in modulation of malignant potency. Our results indicate that human non-small-cell lung cancer cells can autonomously express the mRNAs of uPA, uPAR and PAIs, which are possibly involved in metastasis.
尿激酶型纤溶酶原激活剂(uPA)、其受体(uPAR)及其抑制剂(PAI-1和PAI-2)的转录定位可能与癌症转移有关,但在人类肺癌中尚未确定。为了确定它们在原发性非小细胞肺癌中的调控情况,我们通过Northern印迹分析检测了25例患者的mRNA水平,并通过原位杂交确定了10例患者mRNA的定位。与正常肺组织相比,癌组织中uPA和PAI-2 mRNA的含量显著更高。然而,uPAR和PAI-1 mRNA水平未观察到显著差异。所有转录本均存在于癌细胞中,在一些病例中主要位于肿瘤边缘。此外,相对于高分化癌,PAI-1转录本在低分化和中分化癌中更为丰富,PAI-2转录本在鳞状细胞癌中比在腺癌中更为丰富。因此,PAIs可能参与了恶性潜能的调节。我们的结果表明,人类非小细胞肺癌细胞可以自主表达uPA、uPAR和PAIs的mRNA,这些可能与转移有关。