Role of NGcGM3 Ganglioside in Tumor Biology in Melanoma and Breast Cancer Mouse Models

VALERIA I. SEGATORI; LAURA L. OTERO; DANIEL E. GÓMEZ; DANIEL F. ALONSO; MARIANO R. GABRI

Lake Louise

Simposio; New Frontiers at the Interface of Immunity and Glycobiolgy; 2011

The most common sialic acids in mammals are N-acetyl (NAc) neuraminic acid and N-glycolyl (NGc) neuraminic acid, usually found as terminal constituents of different membrane glycoconjugates such as the GM3 ganglioside. The only structural difference between them consists in a single oxygen atom at the C-5 position of NGc-neuraminic acid, catalyzed by the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH). Although it has been widely reported the presence of NGcGM3 in several human cancers, including melanoma and breast carcinoma, little is known about its role in mouse tumor biology. In mice, we reported the absence of CMAH expression and NGcGM3 in B16 melanoma and F3II mammary carcinoma cell lines. Considering the differences among human and mouse cancer regarding the expression of glycoconjugates, here we explored the role of NGcGM3 in the behaviour of B16 and F3II tumors by promoting its presence in the cell membrane by exogenous incorporation (transient expression) or by transfection of the CMAH enzyme (stable expression). Interestingly, by both strategies, we observed that the presence of NGcGM3 promotes in vitro cell proliferation and adhesion in both cell lines. In addition, both cell lines showed an enhanced tumorigenicity in syngeneic mice only using the transient NGcGM3 expression strategy. When NGcGM3 remained in tumor cells as a result of CMAH transfection, tumorigenicity was reduced in both tumor models. Inoculation of 5x103 control B16 cells per mouse produced palpable melanoma tumors in most animals. On the contrary, at least 2x104 CMAH-transfected B16 cells per mouse were needed to produce the same tumor incidence. Regarding F3II cells, tumor growth rate showed a significant decrease in CMAH-transfected cells in comparison to controls. Tumor volumes at day 39 after inoculation were 60177 and 1,014139 mm3 for controls and CMAH-transfected F3II cells, respectively (p