Nedime Serakıncı
Near East University Medical Faculty, North Cyprus
Title: The double faced role of mesencyhmal stem cells in tumor development and potential use in cancer therapy
Biography
Biography: Nedime Serakıncı
Abstract
Evidences from cancer stem cell biology and the development of new models to validate the self renewal of stem cells are suggesting that stem cells are susceptive to carcinogenesis and consequently can be the origin of many cancers. We have established a telomerase-transduced human Mesenchymal Stem Cell line (hMSC-telo 1) and subsequently exposed these cells to irradiation in order to achieve malignant transformation. Following irradiation we analyzed the long-term effects with special focus on whether irradiation can trigger tumor development in human mesencyhmal stem cells. Our observations indicate that irradiation destabilized the telomeres and that the presence of uncapped telomeres initiated fusion-break-fusion cycles resulting in increased chromosomal instability and tumor formation in MSC’s. Thus, bone marrow derived human mesenchymal stem cells are capable of exhibiting a malignant phenotype. Additionally, hMSC-telo 1 used to investigate whether these cells can preferentially engraft at the tumor site and can be used as vehicles for local delivery of biological agents to the tumor. Our results demonstrated both homing potential of the hMSC by the tumor site occurrence of cellular targeting and also reduction of the tumor size after the pharmacological induction. Mutation of telomere sheltering protein TRF2 or silencing shown to be lethal for the cells thus we made approx. 40% knock-out with siRNA TRF2 in hMSC then the cells subjected to IR. Our results demonstrated controlled suppression (knock-out) of TRF2 1.5-2 fold increase radyosensitivity of hMSC. These results are valuable for improving the effectiveness of radiotherapy in the treatment of cancer.