pGITRL Aktarılan Mezenkimal Kök Hücrelerin Küçük Hücreli Akciğer Kanserine in Vitro Etkisi ve Altın Nanopartiküllerle İşaretlenmesi

Abstract

Glucocorticoid induced tumor necrosis factor receptor (GITR) and its ligand GITRL are members of tumor necrosis factor (TNF) family members. GITR and GITRL found in many cells of cancer microenvironment and can modulate tumor behaviours. Mesenchymal stem cells (MSCs) are non-hemotopoietic stem cells that have capibility to differentiate both mesenchymal and non-mesenchymal origin of various tissues. The modulation of immune response and migration capibilities to the malign tissues makes them good candidates for using them as cellular vehicles for autoimmune and cancer therapy. GITR and GITRL interaction have not been investigated in small cell lung cancer (SCLC) which is an agressive and malign type of tumor. And MSCs have not been used as cellular vehicles. In thesis study, the apoptosis and proliferation of tumor cells were investigated by co-culturing of GITRL transgene carrying MSCs and GITR expressing (SCLC-21H) and not expressing cell lines (NCI-H82). GITRL expressing MSCs were labeled with gold nanoparticles for the in vivo forthcoming studies. In our study, GITR and GITRL protein and mRNA levels were investigated in both MSCs and cancer cells. For MSCs transfection with GITRL, the most efficient system were assessed by using liposomal and electroporation systems. After transfection, both transient and stable transfected MSCs were characterized and co-cultured with SCLC-21H and NCI-H82 cell lines and studied for apoptosis, proliferation and viability. Additionally, they were labeled with gold nanoparticles both in co-culture environment and alone by transmission electron microscopy. In conclusion, GITRL expressing MSCs can change proliferative and apoptotic behaviours of GITR expressing SCLC.