GAL3ST2 from mammary gland epithelial cells affects differentiation of 3T3-L1 preadipocytes.

INTRODUCTION: In the mammary gland, the involution that occurs when lactation ends is an important period for cancer development. We have previously demonstrated stromal-epithelium interactions evaluating conditioned medium of adipose tissue on breast epithelial metalloproteases activity (Creydt et al., Clin Transl Oncol 15:124-131, 2013). Here, we evaluated the effects of conditioned medium of breast epithelial mammary cells on stromal cells.

MATERIALS AND METHODS: Conditioned medium from normal murine mammary gland cell line (NMuMG) and conditioned medium proteins were obtained. Then, they were evaluated on modulation of adipocyte differentiation, using 3T3-L1 cell line.

RESULTS: We described, for the first time, that breast epithelial mammary cells could produce the enzyme galactose 3-O-sulfotransferase 2 (GAL3ST2). Importantly, GAL3ST2 is present in NMMuMG and two human breast cancer cell lines, and it is more strongly expressed in more metastatic tumors. When 3T3-L1 preadipocyte differentiation was triggered in the presence of conditioned medium from NMuMG or GAL3ST2, triglyceride accumulation was decreased by 40 % and C/EBPβ expression by 80 % in adipocytes. In addition, the expression of FABP4 (aP2), another marker of adipocyte differentiation, was inhibited by 40 % in GAL3ST2-treated cells.

CONCLUSIONS: Taken together, these results suggest that GAL3ST2 would interfere with normal differentiation of 3T3-L1 preadipocytes; raising the possibility that it may affect normal differentiation of stromal preadipocytes and be a link to tumor metastatic capacity.