Clinical evaluation of E-cadherin expression and its regulation mechanism in epithelial ovarian cancer.
E-cadherin plays an important role in maintaining tissue architecture. Loss of E-cadherin expression has often been associated with cancer metastasis. This study assessed the immuno-expression of E-cadherin and methylation of CDH1 and correlated them with clinical features in primary epithelial ovarian cancer. Moreover, epithelial ovarian cancer cell SKOV3 was used to explore the mechanism how the demethylating agent 5-Aza inhibited cancer metastasis. Of 80 patients with primary ovarian cancer, we found that decreased immunoexpression pattern of E-cadherin was associated with clinical stage, lymph node metastasis, and degree of differentiation. Methylation of CDH1 detected by MSP occurred frequently and was correlated with reduced expression of E-cadherin protein. 5-Aza treatment could lead to re-expression of functional E-cadherin, followed by decreased MMP-2 and MMP-9 activity and inhibition of cell invasion in SKOV3 cells. Therefore, we conclude that assessment of E-cadherin immunoreactivity or methylation of CDH1 may be a useful prognostic indicator in ovarian cancer, complementary to established prognostic factors. The mechanism underlying 5-Aza's anti-metastasis activity is associated with restored functional expression of E-cadherin and decreased MMPs activity. Correction of aberrant DNA methylation by 5-Aza may provide a new strategy for ovarian cancer prevention and therapy.
Yuecheng
Yu
Y
Department of Obstetrics and Gynecology, Xijing Hospital, Fourth military Medical University, 15 W Changle Road, Xi'an, Shaanxi, 710032, China.
Hongmei
Li
L
Xiaoyan
Xin
X
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000627:therapeutic use; D001943:Breast Neoplasms; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D015820:Cadherins; D017931:DNA Primers; D004273:DNA, Neoplasm; D001374:Azacitidine