Abstract 5286: Enhancing role of tumor cell gangliosides in tumor angiogenesis

Tumor gangliosides, synthesized and shed by many tumors, have a critical role in enhancing tumor formation and progression. Among possible mechanisms of this pro-tumorigenic activity of tumor gangliosides is enhancement of tumor angiogenesis, although directly probing this possibility in vivo has been difficult. Here we tested this hypothesis by exploring the influence of tumor gangliosides on tumor angiogenesis in a unique syngeneic genetic constitutive ganglioside-depleted tumor cell model developed by oncogenic transformation of murine embryonic fibroblasts lacking the key ganglioside synthetic genes, GM3 synthase and GM2 synthase (Oncogene 29:3297-306, 2010). This resulted in complete, selective, and constitutive ganglioside depletion (DKO tumor cells), without reduction in cell proliferation rate. Syngeneic C57BL/6 mice were injected with 104 to106 DKO cells, or with ganglioside-rich wild type (WT) control tumor cells. DKO tumors had remarkably impaired tumor incidence and progression, supporting a role of gangliosides in tumor growth. We also observed striking avascularity of the ganglioside-depleted DKO tumors and therefore probed their state of angiogenesis. By H and E staining, the DKO tumors had many fewer developed vessels (6% of total vessels, vs. 51% in WT tumors, p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5286. doi:1538-7445.AM2012-5286