Baş Boyun Kanserli Hastaların Tükürük Örneklerinden İzole Edilen Eksozom ve Bakterilerin, Sağlıklı Kemik İliği Mezenkimal Kök Hücreler Üzerine Etkilerinin Değerlendirilmesi

Abstract

Recently, in the development of head and neck cancers, the components, which are responsible for the interaction between cells and surrounding healthy tissues, in the tumor microenvironment have become a burgeoning area. The aim of this thesis is to evaluate the effect of salivary exosomes and specific bacterial species (Streptococcus (S.) mitis) isolated from saliva on development of head and neck squamous cell carcinoma. Within the scope of this thesis, isolation of exosomes from saliva samples of head and neck cancer patients/healthy donor was performed and exosomes were characterized by flow cytometry, ELISA and transmission electron microscopy. At the same time, S. mitis was isolated from these clinical samples and characterization analyzes were performed with polymerase chain reaction, optochin-sensitive test and catalase test. By co-culture studies with healthy bone marrow mesenchymal stem cells, cytokine/chemokine/growth factors expressions associated with mesenchymal-epithelial transition were evaluated by cytokine array, CD44 and integrin alpha 6 expressions were evaluated by flow cytometry, and vimentin expressions were evaluated by immunofluorescence analysis. As a result of the data obtained; it was determined that vimentin, integrin alpha 6 and CD44 were expressed in all groups but differed in the S. mitis / MSC co-culture group compared to other groups. When the expressions of cytokine/chemokine/growth factors in co-culture media were evaluated, it was seen that the addition of bacterial flora to exosomes supported the mesenchymal-epithelial transition. This thesis is the first study that evaluates the effects of salivary exosomes and bacteria isolated from the patients with head and neck cancer on the mesenchymal-epithelial transition with co-culture studies and reveals these bio-markers for clinical applications.