Upregulation of caveolin-1 and CD147 expression in nasopharyngeal carcinoma enhanced tumor cell migration and correlated with poor prognosis of the patients.
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.
Du
Zi-Ming
ZM
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Hu
Chun-Fang
CF
Shao
Qiong
Q
Huang
Ma-Yan
MY
Kou
Chang-Wei
CW
Zhu
Xiao-Feng
XF
Zeng
Yi-Xin
YX
Shao
Jian-Yong
JY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
C497886:BSG protein, human; C495540:CAV1 protein, human; D051242:Caveolin 1; D012333:RNA, Messenger; D051926:Basigin; D053507:Matrix Metalloproteinase 11; D019278:Matrix Metalloproteinase 3