Slug Is Associated With Tumor Metastasis and Angiogenesis in Ovarian Cancer

Abstract

Ovarian cancer is the most lethal gynecologic malignancy among women and usually initiated by the malignant transformation of epithelial cells. The progression of ovarian cancer involves a cascade of events, including tumor cell epithelial–mesenchymal transition (EMT), invasion, migration, and angiogenesis. Slug plays vital roles in the development of motile and invasive manner of cancer cells via EMT progression. The present work is devoted to investigate the effect of slug on the invasion and angiogenesis in ovarian cancer. The findings reveal that tumors with high expression of slug (44 of 60) represent higher tumor grade, lymph node metastasis, and worse prognosis than those with low expression (16 of 60; P < .05). We also identified a significant correlation between the slug and the microvessel density (MVD). Results of transwell migration assay showed that decreased slug induced by short hairpin RNA contributed to the repressed invasion and migration of SKOV3 cells. Additionally, the migration and tube formation capacity of human umbilical vein endothelial cells were markedly decreased in SKOV3-sh-conditioned medium compared to SKOV3 and SKOV3-NC. Furthermore, xenograft mouse models (SKOV3/SKOV3-sh cells injection into BALB/c nude mice) were developed to validate the effects of slug. The data confirmed that inhibited expression of slug extensively decreased the growth of tumor and MVD in vivo. Moreover, knockdown of slug can significantly reduce tumor angiogenesis of SKOV3 cells via ccn1/vascular endothelial growth factor. Thus, our present study demonstrates that slug is closely associated with tumor metastasis and angiogenesis in ovarian cancer.