G_D3 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.