Expression of plasminogen activator inhibitors 1 and 2 in lung cancer and their role in tumor progression
| Autor: | Robert C, Isabelle Bolon, Gazzeri S, Veyrenc S, Brambilla C, Brambilla E |
|---|---|
| Přispěvatelé: | gazzeri, sylvie, INSERM U1209, Institute for Advanced Biosciences |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Lung Neoplasms
Serine Proteinase Inhibitors Serine Proteinase Inhibitors/biosynthesis [SDV]Life Sciences [q-bio] Urokinase-Type Plasminogen Activator/biosynthesis [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.CAN] Life Sciences [q-bio]/Cancer Carcinoma Non-Small-Cell Lung Plasminogen Activator Inhibitor 1 Plasminogen Activator Inhibitor 2 Humans [SDV.BC] Life Sciences [q-bio]/Cellular Biology In Situ Hybridization Neoplasm Staging Fibroblasts/metabolism Plasminogen Activator Inhibitor 1/biosynthesis Carcinoma Non-Small-Cell Lung/metabolism Plasminogen Activator Inhibitor 2/biosynthesis Fibroblasts Urokinase-Type Plasminogen Activator Immunohistochemistry Carcinoma Neuroendocrine [SDV] Life Sciences [q-bio] Disease Progression Carcinoma Neuroendocrine/metabolism Lung Neoplasms/metabolism |
| Zdroj: | Clinical Cancer Research Clinical Cancer Research, American Association for Cancer Research, 1999, 5 (8), pp.2094-102 Europe PubMed Central Clinical Cancer Research, Vol. 5, No 8 (1999) pp. 2094-2102 |
| ISSN: | 1078-0432 1557-3265 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|