Upregulation of caveolin-1 and CD147 Expression in Nasopharyngeal Carcinoma Enhanced Tumor Cell Migration and Correlated With Poor Prognosis of the Patients

Int J Cancer. 2009 Oct 15;125(8):1832-41. doi: 10.1002/ijc.24531.

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 = 0.025 and 0.017, respectively) and a lower 5-year survival rate (p = 0.02 and 0.0009, respectively). In addition, Cav-1 expression levels correlated significantly with local recurrence (p = 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 = 2.135; p = 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 (rho = 0.330, p = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Basigin / genetics
  • Basigin / metabolism*
  • Caveolin 1 / antagonists & inhibitors
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Movement*
  • Female
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 11 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Middle Aged
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Cells, Cultured
  • Up-Regulation / physiology*
  • Young Adult

Substances

  • BSG protein, human
  • CAV1 protein, human
  • Caveolin 1
  • RNA, Messenger
  • Basigin
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinase 3