Abstract B27: Activin A induces vascular endothelial cell proliferation and angiogenesis in oral cancer

Abstract

Solid tumors must develop direct and indirect ways to induce angiogenesis in order to continue progression and expansion. The expression of angiogenic factors in the tumor microenvironment is a complex process involving interactions among different cell types. Previous studies demonstrated activin A, a member of the TGF-β superfamily, participates in the development and progression of oral squamous cell carcinomas (OSCC) via regulation of the tumor microenvironment, but its effects in the modulation of angiogenesis are unknown. We examined whether activin A, recombinant or derivate from OSCC cells, promotes angiogenesis of the human umbilical vein endothelial cells (HUVECs). Activin A-treated cells increased tubulogenesis activity concomitantly with high cellular proliferation and low apoptosis. Conversely, follistatin, an activin A antagonist, and activin A knock down in HUVECs significantly inhibited proliferation, induced apoptosis and decreases tube formation. Similarly, conditioned media harvested from OSCC cells expressing high activin A levels increased the proliferative rate and the tubulogenic activity of HUVECs more than those obtained from OSCC cells expressing a shRNA to neutralize activin A expression. In conclusion, our results show that activin A derived from OSCC cells promotes endothelial cell proliferation and tumor angiogenesis, suggesting that activin A signaling could be an important target for tumor vascular disruption in oral cancer. Financial support: FAPESP #2013/19856-2 and #2013/01607-6. Citation Format: Carine Ervolino de Oliveira, Nilva de Karla Cervigne, Carolina Carneiro Souza Macedo, Adriana Franco Paes Leme, Edgard Graner, Ricardo Della Coletta. Activin A induces vascular endothelial cell proliferation and angiogenesis in oral cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B27.

Influence of Diabetes Mellitus Type 2 on the angiogenic potential of Bone Marrow derived Mesenchymal Stem Cells

“…However, the role of Activin A in angiogenesis is controversial [36]. While it was demonstrated to inhibit the cellular growth of vascular endothelial cells [37][38][39], contrasting findings showed that Activin A induced vascular endothelial cells proliferation [40]. Supporting this observation, Activin A was also found to induce VEGF expression leading to recruitment of blood vessels in vitro [41].This discrepancy of the pro-and anti-angiogenic role of activin A can be explained by the dual role of TGF-β [39]which share the Smad intracellular signalling proteins with TGF-β [42].…”