Upregulation of caveolin‐1 and CD147 expression in nasopharyngeal carcinoma enhanced tumor cell migration and correlated with poor prognosis of the patients

Abstract

Expression of caveolin-1 (Cav-1) and extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) and their prognostic significance were analyzed in archive NPC samples. Cav-1 and CD147 were overexpressed in 49. 48% (96/194) and 59.39% (117/ 197) of NPC, respectively. Both Cav-1 and CD147 expression levels correlated significantly with metastasis (p 5 0.025 and 0.017, respectively) and a lower 5-year survival rate (p 5 0.02 and 0.0009, respectively). In addition, Cav-1 expression levels correlated significantly with local recurrence (p 5 0.038). Multivariate Cox regression analysis indicated that combination of high Cav-1 and CD147 expression was a significant, independent prognosis predictor in patients with NPC (HR 5 2.135; p 5 0.006). Functional studies revealed that overexpression of Cav-1 promoted secretion of MMP-3 and MMP-11 (active) proteins, as well as an increase in the migratory ability of CNE1 and CNE2 cells, while siRNA-mediated silencing of Cav-1 or CD147 led to reduced levels of MMP-3 and MMP-11(active) secretion, and reduced migration capacity of CNE1 and CNE2 cells. We observed a positive correlation between Cav-1 and CD147 expression in NPC (q 5 0.330, p 5 0.000), CD147 protein levels were upregulated in Cav-1 overexpressing CNE1 and CNE2 cells, whereas siRNA-mediated silencing of Cav-1 led to the downregulation of CD147 expression. Our results indicate that Cav-1 and CD147 overexpression predict poor NPC prognosis and enhanced tumor cell migration, which is associated with MMP-3 and MMP-11 (active) secretion. ' 2009 UICC

Caveolin-1 in Melanoma Progression

“…Moreover, studies in samples derived from esophageal squamous cell carcinoma (Ando, Ishiguro et al 2007), small cell lung carcinomas , colon cancer cells with elevated metastatic potential ( (Bender, Reymond et al 2000), see below) and gastric cancer (Burgermeister, Tencer et al 2003), revealed that caveolin-1 expression correlates with poor patient prognosis. Furthermore, caveolin-1 is also overexpressed in nasopharyngeal carcinoma and protein levels correlate there with poor prognosis, enhanced tumor cell migration and metastasis (Du, Hu et al 2009). Finally, caveolin-1 was recently associated with tumor progression in a panel of melanoma cell lines, since increased expression correlated with enhanced proliferation, cell migration and tumorigenicity (Felicetti, Parolini et al 2009).…”

Enhanced Meta-analysis Highlights Genes Involved in Metastasis from Several Microarray Datasets

“…CAV1 (caveolin 1, caveolae protein, 22kDa) plays a role in the formation of caveolae that are small lipid rafts responsible for vesicle trafficking, cholesterol homeostasis and signal transduction. High CAV1 levels have been linked with the metastatic phenotype as they lead to the secretion of MMP3 and MMP11 (matrix metalloproteinases 3 and 11) [30]. High CAV1 levels are also observed in MDA-MB-231 cells compared to MCF-7 cells in the expression profile in Figure 4F.…”

Expression of Cav-1 in tumour cells, rather than in stromal tissue, may promote cervical squamous cell carcinoma proliferation, and correlates with high-risk HPV infection

“…Even in the same histology type such as SCC, Cav-1 also has a different expression pattern. In vivo study of tongue (7), esophagus (8,18), bladder (21), lung (22) and nasopharynx (23) SCC demonstrated overexpression of Cav-1 protein in the tumour cells, and is closely correlated with tumor progression and poor prognosis (18,23). Nevertheless, in the primary head and neck squamous cell carcinoma (HNSCC), Cav-1 may play an inhibitory role in tumourigenesis and lung metastasis (24).…”