GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells

Abstract

The disialoganglioside G(D3) is an oncofetal marker of a variety of human tumors including melanoma and neuroblastoma, playing a key role in tumor progression. G(D3) and 9-O-acetyl-G(D3) are overexpressed in approximately 50% of invasive ductal breast carcinoma, but no relationship has been established between disialoganglioside expression and breast cancer progression. In order to determine the effect of G(D3) expression on breast cancer development, we analyzed the biosynthesis of gangliosides in several breast epithelial cell lines including MDA-MB-231, MCF-7, BT-20, T47-D, and MCF10A, by immunocytochemistry, flow cytometry, and real-time PCR. Our results show that, in comparison to tumors, cultured breast cancer cells express a limited pattern of gangliosides. Disialogangliosides were not detected in any cell line and G(M3) was only observed at the cell surface of MDA-MB-231 cells. To evaluate the influence of G(D3) in breast cancer cell behavior, we established and characterized MDA-MB-231 cells overexpressing G(D3) synthase. We show that G(D3) synthase expressing cells accumulate G(D3), G(D2), and G(T3) at the cell surface. Moreover, G(D3) synthase overexpression bypasses the need of serum for cell growth and increases cell migration. This suggests that G(D3) synthase overexpression may contribute to increasing the malignant properties of breast cancer cells.