Snail is critical for tumor growth and metastasis of ovarian carcinoma.
Snail, a key inducer of epithelial-mesenchymal transition (EMT), plays an important role in cancer metastasis. To better understand the role of Snail in the metastasis of ovarian carcinoma, expression of Snail was knocked down by antisense-Snail in the highly metastatic ovarian cancer cell line HO8910PM. Gene array analysis revealed that blocking Snail expression suppressed the activity of matrix metalloproteinases (MMPs) and upregulated TIMP3, an MMP inhibitor. These findings suggest that Snail interacts with MMP during tumor invasion and metastasis. In addition, we examined the role of Snail in an ovarian cancer orthotopic model by using the antisense-Snail HO8910PM cell line. We found that the size of primary ovarian cancer tumor and the number of metastatic lesions were significantly reduced when Snail was knocked down. Confirming our initial findings, the activity of MMP2 was greatly inhibited in tumors from antisense-Snail cells. Furthermore, immunohistochemical analysis on ovarian cancer progression tissue array demonstrated that the expression of Snail was significantly higher in metastatic lesions, and Snail expression correlated with the stage of ovarian cancer. Interestingly, in early-stage tumors, Snail was localized in both the cytoplasm and nucleus. In late stage and metastatic lesions, the level of Snail was elevated, and Snail was localized to the nucleus. The expression level and nuclear localization of Snail were also inversely correlated with E-cadherin expression. Overall, our study indicates that Snail plays a critical role in tumor growth and metastasis of ovarian carcinoma through regulation of MMP activity.
Jin
Hongyan
H
Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.
Yu
Yinhua
Y
Zhang
Tao
T
Zhou
Xianrong
X
Zhou
Jiayi
J
Jia
Luoqi
L
Wu
Yadi
Y
Zhou
Binhua P
BP
Feng
Youji
Y
D000328:Adult; D000368:Aged; D000818:Animals; D015820:Cadherins / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*
D015820:Cadherins; D000071250:Snail Family Transcription Factors; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D014157:Transcription Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9