M2-polarized macrophages in keratocystic odontogenic tumor: relation to tumor angiogenesis

The purpose of this study was to evaluate the presence of M2-polarized macrophages and their relationships to angiogenesis in keratocystic odontogenic tumor (KCOT). M2-polarized macrophages were detected in KCOT samples by immunohistochemistry and immunofluorescence. Meanwhile, microvessel density measured with antibody against CD31 was closely correlated with the presence of M2-polarized macrophages. In addition, macrophage colony-stimulating factor (M-CSF) significantly contributed to the activation of M2-polarized macrophages. Moreover, the results of in vitro wound healing, cell migration and tube formation assays further revealed the pro-angiogenic function of M2-polarized macrophage-like cells. This function might be associated with secretion of angiogenic cytokines, such as vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta) and matrix metalloprotein-9 (MMP-9). This study demonstrates for the first time that M2-polarized macrophages are prevalent in KCOT, and their presence is dependent on M-CSF expression. More importantly, these tumor-supportive cells can also promote tumor angiogenesis by secreting angiogenic cytokines.