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. Ithas been shown, in animal models, that MSCs derived from bone marrow, producingTNF-related apoptosis-inducing ligand (TRAIL), inhibit the growth of tumors that metastatizeto the bone tissue, including lung cancer; however, the expression of TRAIL bythe MSCs to be effective, must be stimulated with genetic engineering techniques withthe involvement of bacterial vectors. TRAIL is a pro-apoptotic factor, member of thesuper-family of tumor necrosis factors, known for its peculiarity to selectively induceapoptosis in cancer cells. TRAIL can activate apoptotic signals by binding two differentdeath receptors, DR4 and DR5. In our work we evaluated the production of TRAIL byDPSCs differentiated toward the osteoblastic phenotype. Microarray experiments, alsosupported by real-time PCR, showed that in DPSCs after differentiation, the expressionof TRAIL increased fifteen times. Moreover, cell viability tests have shown that DPSCsdifferentiating into osteoblasts become resistant to the pro-apoptotic effect of the molecule.This strong resistance derives from a significant decrease in the expression ofTRAIL receptors DR4 and DR5, and is confirmed by the weak activation of intracellularapoptotic signal (caspase 3) following the exposure to the molecule. Conversely, thetumor cell lines expressed high levels of DR4 and DR5, and in the presence of TRAIL,activate the intracellular apoptotic signals (caspase 3-8). Thus, the DPSCs, differentiatedinto osteoblasts, expressing high levels of TRAIL and developing a resistance tothe apoptotic effect of the molecule, could represent a valuable therapeutic approach tocancer therapy.
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
Ballini, A;
2010-01-01
Abstract
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. Ithas been shown, in animal models, that MSCs derived from bone marrow, producingTNF-related apoptosis-inducing ligand (TRAIL), inhibit the growth of tumors that metastatizeto the bone tissue, including lung cancer; however, the expression of TRAIL bythe MSCs to be effective, must be stimulated with genetic engineering techniques withthe involvement of bacterial vectors. TRAIL is a pro-apoptotic factor, member of thesuper-family of tumor necrosis factors, known for its peculiarity to selectively induceapoptosis in cancer cells. TRAIL can activate apoptotic signals by binding two differentdeath receptors, DR4 and DR5. In our work we evaluated the production of TRAIL byDPSCs differentiated toward the osteoblastic phenotype. Microarray experiments, alsosupported by real-time PCR, showed that in DPSCs after differentiation, the expressionof TRAIL increased fifteen times. Moreover, cell viability tests have shown that DPSCsdifferentiating into osteoblasts become resistant to the pro-apoptotic effect of the molecule.This strong resistance derives from a significant decrease in the expression ofTRAIL receptors DR4 and DR5, and is confirmed by the weak activation of intracellularapoptotic signal (caspase 3) following the exposure to the molecule. Conversely, thetumor cell lines expressed high levels of DR4 and DR5, and in the presence of TRAIL,activate the intracellular apoptotic signals (caspase 3-8). Thus, the DPSCs, differentiatedinto osteoblasts, expressing high levels of TRAIL and developing a resistance tothe apoptotic effect of the molecule, could represent a valuable therapeutic approach tocancer therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
