témavezető: Kókai Endre
helyszín (magyar oldal): DE ÁOK Orvosi Vegytani Intézet helyszín rövidítés: DEOVI
A kutatási téma leírása:
Tumor associated macrophages (TAM) are considered as a key regulator of tumoral microenvironment. Intercellular interactions of TAMs with various immune- and tumor cells are responsible for the formation of prosperous milieu for tumor growing and invasion. Activated macrophages biologically classified into two subgroups: classically activated macrophages (M1) and alternative activated macrophages (M2). In the early stage of the cancer development TAMs show M1-like phenotype characterized by high IL-12 releases that cause tumor cell disruption. However, macrophages change during tumor development and in late-stage of tumor progression, TAMs exhibit an M2-like phenotype characterized by reduced antitumoral activity. It has been shown that PI3Kγ highly expresses in myeloid cells but not in cancer cells and PI3Kγ signaling through Akt and mTOR controls a macrophage switch between immune stimulation and suppression.
TAMs secrete growth factors during spheroid formation in order to support tumor cell proliferation. TAMs express large amount of epidermal growth factor (EGF) and the activation of EGF receptor (EGFR) on tumor cells results integrin/intercellular adhesion molecule-1 (ICAM-1) expression through VEGFR3 signaling and promote tumor spheroid formation.
The primary aim of this program is to establish the culturing of multicellular tumor spheroids (MCTS) in the presence of differently polarized macrophages in our laboratory. The MCTS will serve as a three-dimensional (3D) model for the investigation of a 3D analysis of tumor-associated migration and differentiation processes of macrophages; the micro-environmental regulation of tumor cell proliferation in the presence of PI3Kγ inhibitors; the molecular regulation of EGF production of TAM cells.
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