MT3-MMP down-regulation promotes tumorigenesis and correlates to poor prognosis in esophageal squamous cell carcinoma.
The membrane-type matrix metalloproteinases (MT-MMPs) play an important role in degrading the extracellular matrix (ECM) and facilitating protease-dependent tumor progression and invasion. Here, we report that unlike MT1-MMP, MT3-MMP was down-regulated in esophageal squamous cell carcinoma (ESCC) as detected by real-time PCR (qPCR), Western blot analysis, and immunohistochemistry (IHC). Down-regulation of MT3-MMP was observed at protein level in 66.3% of ESCC specimens (by IHC, n = 86) for routine pathologic diagnosis, as well as at mRNA level in 63.3% of surgically resected ESCC tumors paired with surrounding nontumor tissues (by qPCR, n = 30). Notably, MT3-MMP down-regulation significantly correlated with lymph node metastasis and poor overall survival of patients with ESCC (median 5-year survival = 50.69 vs. 30.77 months for patients with MT3-MMP-negative and -positive ESCC, respectively). Mechanistically, MT3-MMP negatively regulated proliferation, colony formation, and migration of ESCC cells, in association with cell cycle arrest at G1, due to up-regulation of p21(Cip1) and p27(Kip1) . Together, as a tumor suppressor in ESCC, MT3-MMP down-regulation represents an unfavorable factor for prognosis of patients with ESCC.
Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. zengfuxue@aliyun.com.
Zengfu
Z
Xue
Department of Pharmacy, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Xiumin
X
Wu
Department of Medical Oncology, The Affiliated Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.
Xiong
X
Chen
Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. zfxue@xmu.edu.cn.
Qi
Q
Luo
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D053513:Matrix Metalloproteinase 16 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference
C507102:MMP16 protein, human; D053513:Matrix Metalloproteinase 16
Cell cycle; MT3-MMP; esophageal squamous cell carcinoma; immunohistochemistry; prognosis