Ability Of Cervical Cancer Cells Research Articles

SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway

Objectives Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as Wnt antagonists and play important implications in carcinogenesis. Recently, we have shown that SFRP1 and SFRP2 are frequently downregulated through promoter hypermethylation. However, the function of SFRP1 and SFRP2 in cervical cancer remains unclear. Methods To improve our understanding of the role of SFRP1 and SFRP2 in cervical cancer cells, we use overexpression or shRNA approach in cervical cancer cell lines. Results Restoration of the expression of SFRP1 and SFRP2 attenuated Wnt signaling in CaSki cells, decreased abnormal accumulation of free β-catenin in the nucleus, and suppressed cancer cell growth. In addition, different statuses of β-catenin accumulation in the cytoplasm of CaSki or HeLa3rd cells were observed, suggesting that different Wnt pathways are executed. Furthermore, we demonstrated that SFRP1 and SFRP2 enhance the expression of the epithelial marker E-cadherin, through inhibition of the expression of SLUG, TWIST and SNAIL, three transcription factors involved in the epithelial mesenchymal transition (EMT) program. Finally, in a xenograft animal model, we showed that SFRP1 suppresses tumorigenicity of cancer cells in vivo. Conclusions Taken together, these data strongly suggest that epigenetic silencing of SFRP genes leads to oncogenic activation of the Wnt pathway and contributes to cervical cancer progression through the EMT program.

Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells

Constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumors. MMPs are a family of zinc endopeptidases consisting of at least 20 different members. In particular, MMP-2 and MMP-9 are reported to be closely associated with invasion and metastasis in several cancers. We investigated whether expression of MMP-2 and MMP-9 is associated with invasion ability of seven cervical cancer cells by administration of o-phenanthroline as MMP inhibitor. In two cell lines, Siha and Caski, MMP-2 mRNA and protein were expressed at high levels. After treatment with o-phenanthroline, the rate of invasion in these two cell lines was significantly decreased. In contrast, in the other two cell lines, HT-3 and Caski, high levels of MMP-9 mRNA and protein were expressed but there was no decrease in the rate of invasion in these cells after treatment with o-phenanthroline. The data suggest that expression level of MMP-2 mRNA may regulate with invasion ability of cervical cancer.