HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Expression of plasminogen activator inhibitors 1 and 2 in lung cancer and their role in tumor progression.

Abstract
The plasminogen activator cascade initiated by urokinase type plasminogen activator (u-PA) is involved in extracellular matrix degradation during the tumor invasion process. The plasminogen activator inhibitors 1 (PAI-1) and 2 (PAI-2) are two specific inhibitors of u-PA. We hypothesized that the balance between u-PA and its two inhibitors could be disrupted to favor plasminogen activation during lung cancer progression. Using immunohistochemistry, we analyzed the pattern of expression of u-PA, PAI-1, and PAI-2 in non-small cell lung carcinomas (NSCLC) and neuroendocrine (NE) lung tumors. u-PA and PAI-1 were both detected in stromal fibroblasts and in tumor cells. In 84 NSCLCs, their epithelial expression was strongly correlated and linked to the presence of node metastasis (P = 0.008), whereas their coexpression in fibroblasts was associated with larger tumor size (P = 0.04) and advanced stages (P = 0.009). In 72 NE tumors, u-PA and PAI-1 were more frequently expressed in fibroblasts in high-grade NE tumors (SCLC and large cell NE tumors) than in low- and intermediate-grade tumors (typical and atypical carcinoids). Comparison of in situ hybridization and immunohistochemistry in 14 cases showed that PAI-1 was consistently expressed by stromal fibroblasts, although the protein was also localized in tumor cells. In contrast, the expression of PAI-2 was restricted to fibroblasts and correlated with the absence of nodal involvement (P = 0.005). Considering NE tumors, the frequency of PAI-2 expression decreased along the NE spectrum from typical carcinoids to SCLCs. These data suggest that PAI-lacts in synergy with u-PA to favor tumor invasion process and connotes aggressivity, in contrast with PAI-2, which may block u-PA-mediated proteolysis and is inversely correlated with tumor progression.
AuthorsC Robert, I Bolon, S Gazzeri, S Veyrenc, C Brambilla, E Brambilla
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 5 Issue 8 Pg. 2094-102 (Aug 1999) ISSN: 1078-0432 [Print] UNITED STATES
PMID10473092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Serine Proteinase Inhibitors
  • Urokinase-Type Plasminogen Activator
Topics
  • Carcinoma, Neuroendocrine (metabolism)
  • Carcinoma, Non-Small-Cell Lung (metabolism)
  • Disease Progression
  • Fibroblasts (metabolism)
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lung Neoplasms (metabolism)
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 (biosynthesis)
  • Plasminogen Activator Inhibitor 2 (biosynthesis)
  • Serine Proteinase Inhibitors (biosynthesis)
  • Urokinase-Type Plasminogen Activator (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: