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Dental Pulp Stem Cells (DPSCs), differentiating into osteoblasts, become a source of the pro-apoptotic factor TRAIL: evaluation of an experimental model for cancer therapy

Authors
Publisher
Italian Journal of Anatomy and Embryology
Publication Date
Keywords
  • Dpscs
  • Stem Cells
  • Trail
  • Osteoblast Differentiation
  • Cancer Cells Apoptosis
Disciplines
  • Engineering
  • Medicine

Abstract

IJAE Vol. 115, n. 1/2 (Supplement), 2010 119 Dental Pulp Stem Cells (DPSCs), differentiating into osteoblasts, become a source of the pro-apoptotic factor TRAIL: evaluation of an experimental model for cancer therapy Giorgio Mori1, Giacomina Brunetti2, Angela Oranger2, Francesca Sardone2, Claudia Carbone2, An- drea Ballini3, Roberto Grassi3, Silvia Colucci2, Maria Grano2 1 Dipartimento di Scienze Biomediche, Università di Foggia, Italy 2 Dipartimento di Anatomia Umana e Istologia “Rodolfo Amprino”, Università di Bari Italy 3 Dipartimento di Odontostomatologia e Chirurgia, Università di Bari Italy The DPSCs belong to the family of mesenchymal stem cells (MSCs) and are capable, if properly stimulated to differentiate into different cell types including osteoblasts. It has been shown, in animal models, that MSCs derived from bone marrow, producing TNF-related apoptosis-inducing ligand (TRAIL), inhibit the growth of tumors that met- astatize to the bone tissue, including lung cancer; however, the expression of TRAIL by the MSCs to be effective, must be stimulated with genetic engineering techniques with the involvement of bacterial vectors. TRAIL is a pro-apoptotic factor, member of the super-family of tumor necrosis factors, known for its peculiarity to selectively induce apoptosis in cancer cells. TRAIL can activate apoptotic signals by binding two different death receptors, DR4 and DR5. In our work we evaluated the production of TRAIL by DPSCs differentiated toward the osteoblastic phenotype. Microarray experiments, also supported by real-time PCR, showed that in DPSCs after differentiation, the expression of TRAIL increased fifteen times. Moreover, cell viability tests have shown that DPSCs differentiating into osteoblasts become resistant to the pro-apoptotic effect of the mol- ecule. This strong resistance derives from a significant decrease in the expression of TRAIL receptors DR4 and DR5, and is confirmed by the weak activation of intracellular apoptotic signal (cas

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