Ewing’s Sarcoma is a pediatric bone cancer that has only a 30% five-year survival rate despite aggressive treatments with chemotherapy, radiation and surgery.  Cannabinoids, compounds similar in structure to tetrahydrocannabinol (THC) from the marijuana plant, have demonstrated anti-inflammatory, antiemetic, and analgesic effects as well as the ability to decrease tumor cell viability and growth. While THC is psychoactive, ajulemic acid (AJA), a synthetic cannabinoid, and cannabidiol (CBD), a naturally occurring cannabinoid, are not, making them viable potential treatments for Ewing’s sarcoma. Both AJA and CBD decrease cell viability in Ewing’s cell lines and spheroids and inhibit angiogenesis in vitro, but the conventional CB1 and CB2 cannabinoid receptors do not seem to mediate these effects. In an effort to elucidate the mechanisms through which these cannabinoids affect tumorigenesis, mass spectrometry was performed on cell lysates from untreated, AJA-treated, and CBD-treated Ewing’s sarcoma cells. Endoglin (ENG), an accessory receptor for transforming growth factor beta (TGF-β, was found to be downregulated in both AJA- and CBD-treated samples as compared to the untreated controls.  ENG is a homodimeric transmembrane glycoprotein that is upregulated in proliferating endothelial cells and has been suggested as marker for tumor-related angiogenesis.  The formation of new blood vessels is essential for tumor growth and metastasis; therefore, inhibition of tumor angiogenesis may improve outcomes in patients with solid tumors.  This study utilized computational docking methods to investigate potential cannabinoid binding to ENG and the TGF-β receptor complex and ELISA to confirm differential regulation of ENG in Ewing’s sarcoma cells.

Effects of cannabinoids on TGFβ-complex protein, endoglin, in Ewing’s sarcoma

253rd National Meeting (2017)

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