Phd candidate Seoul national university Seoul, Kyonggi-do, Republic of Korea
Abstract: Background – Tumor associated macrophages (TAMs) act multi-functional roles in tumor progression, immune regulation, metastasis, angiogenesis and chemoresistance. Hypoxia in the tumor microenvironment induces M2 polarization of TAMs, which enhances chemoresistance. Hypothesis/Objectives – In this study, a hybrid spheroid model of canine mammary gland tumor (MGT) cell lines (CIPp, CIPm) and canine macrophages (DH82) was established to mimic tumor microenvironment. We aim to investigate the effects of hypoxia induced by the spheroids model on the chemoresistance of canine MGT cells. We also wanted to investigate the interactions between canine MGT cells and macrophages under doxorubicin. Animals – This study didn’t use animals. Methods – In vitro study. Hybrid spheroids was created using ultra low adhesion plate. The interactions between canine MGT cells and macrophages were investigated through gene expression, cell viability, apoptosis, and cell cycle arrest. Results – We confirmed the effects of hypoxia on the growth factors and multi-drug resistance of canine MGT cells in the spheroid model. Moreover, infiltration of M2 polarized macrophage in the spheroid model was identified. Finally, we confirmed that macrophages induce chemoresistance by examining the effects of doxorubicin on growth, apoptosis, cell cycle arrest, and multi-drug resistance gene expression in canine MGT cells. Conclusions and clinical importance – We suggest that the crosstalk between macrophages and canine MGT cells contributes to chemoresistance in tumor cells, thus indicating that macrophages are an important factor in tumor cell resistance to anti-cancer drugs. The hybrid spheroid model can be applied to anti-cancer drug research in the future.
