Role of zinc transporter LIV-1 protein in high-grade serous ovarian cancer
High-grade serous carcinoma (HGSC) of the ovary is the most lethal gynecological cancer. Although recent progress has advanced our understanding in the aggressiveness of HGSC, the molecular mechanisms involved in the development of this cancer remain unclear. One of the main features of aggressive tumours is their ability to metastasize. In general, epithelial ovarian cancers (EOCs) spread through local extension, lymphatic invasion, and intraperitoneal implantation. Studies have suggested that the zinc transporter LIV-1 protein has an important role in tumour metastasis in different tissues. However, there are no reports on the role of LIV-1 in HGSC metastasis. We investigated the role of LIV-1 in the invasive and migration potential of HGSC cells. We observed variable expression levels of the LIV-1 gene and protein in 14 HGSC cell lines. Although a positive correlation was observed between the gene expression and the quantities of LIV-1 protein, this correlation was not strong and not significant; thus, we chose five cell lines to perform biological assays, based on their protein levels: TOV3133G and TOV2295(R) (high), TOV2978G (medium), and TOV1369 and OV866(2) (low). We found that there was a strong and significant positive correlation between LIV-1 levels and the invasive potential of these HGSC cells (R2 = 0.8666, p = 0.0216), but a weak and negative correlation (not significant) with their migration potential (R2 = 0.4514, p = 0.2142). RNAi experiments demonstrated that reduced LIV-1 expression inhibits invasive capacity; however, no significant differences were observed in regard to migration capacity. Our results suggest that LIV-1 has a positive role in favouring the tumour progression of HGSC. We have demonstrated that LIV-1 is involved in the in vitro invasion but not migration of HGSC cells, and that its expression is associated with more aggressive ovarian cancers,suggesting LIV-1 as a potential marker for tumour aggressiveness.
LIV-1 Cell invasion Cell migration Epithelial ovarian cancer High-grade serous carcinoma (HGSC)