Inhibiting the growth of tumor vasculature represents one of the relevant strategies against tumor progression. Between all the different pro-angiogenic molecular targets, plasma membrane glycosphingolipids have been under-investigated. In this present study, we explore the anti-angiogenic therapeutic advantage of a tumor immunotherapy targeting the globotriaosylceramide Gb3. In this purpose, a monoclonal antibody against Gb3, named 3E2 was developed and characterized. We first demonstrate that Gb3 is over-expressed in proliferative endothelial cells relative to quiescent cells. Then, we demonstrate that 3E2 inhibits endothelial cell proliferation in vitro by slowing endothelial cell proliferation and by increasing mitosis duration. Antibody 3E2 is further effective in inhibiting ex vivo angiogenesis in aorta ring assays. Moreover, 3E2 treatment inhibits NXS2 neuroblastoma development and liver metastases spreading in A/J mice. Immunohistology examination of the NXS2 metastases shows that only endothelial cells, but not cancer cells express Gb3. Finally, 3E2 treatment diminishes tumor vessels density, proving a specific therapeutic action of our monoclonal antibody to tumor vasculature. Our study demonstrates that Gb3 is a viable alternative target for immunotherapy and angiogenesis inhibition.
Citation: Desselle A, Chaumette T, Gaugler M-H, Cochonneau D, Fleurence J, et al. (2012) Anti-Gb3 Monoclonal Antibody Inhibits Angiogenesis and Tumor Development. PLoS ONE 7(11): e45423. doi:10.1371/journal.pone.0045423
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Image: Gb3 immunolocalization in HMEC-1 by FITC-conjugated 3E2 (green; upper panel) vs. control isotypic 11E10 IgM (lower panel) and counterstaining with Draq5. Scale bar represent 20 µm.