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

Abstract

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-β (TGF-β) 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.

Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway

“…Endometrial tissue homogenates were prepared as previously described [ 17 ]. Each of 10 frozen endometrial tissue samples (200 mg) was immediately placed in 5 ml of serum-free RPMI 1640 medium and homogenized in a glass homogenizer.…”

The effect of healing phenotype-inducing cytokine formulations within soft hydrogels on encapsulated monocytes and incoming immune cells

“…A majority of the activated cells gained nonspherical, irregular morphology, and a smaller portion was elongated. According to some researchers, M2-type macrophages have mixed irregular and elongated morphology with predominant elongated morphology 11,13 although the inuence of encapsulation in a 3D scaffold has not been fully explored by them. However, deducing the polarization stage of macrophages from their morphology can be misleading since the morphology is highly variable and inuenced by many factors.…”

“…Later, the M1-type macrophages switch to the M2-type macrophages, which contribute to tissue repair by releasing various growth factors and cytokines that promote angiogenesis and cell proliferation. 9,10 Macrophage differentiation and polarization in vitro can be promoted by the signals observed in vivo: the monocytes are activated by M-CSF (for M2) or GM-CSF (for M1) [11][12][13] and then polarized by the cytokines. Usually, IFN-g, TNF-a and bacterial lipopolysaccharide (LPS) are used for M1 polarization, whereas IL-4 and IL-13 or IL-10 are used for M2 polarization.…”

N-Terminal Modification of the Tetrapeptide Arg-Leu-Tyr-Glu, a Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) Antagonist, Improves Antitumor Activity by Increasing its Stability against Serum Peptidases

“…VEGF-A enhances infiltration of macrophages into tumors via activation of VEGFR-2 (Wheeler et al, 2018), as well as stimulates the polarization of TAMs from the cytotoxic M1 to the angiogenic M2 phenotype (Riabov et al, 2014). M2 polarization contributes to a detrimental tumor microenvironment via VEGF expression and immune suppression (Mazibrada et al, 2008;Zhong et al, 2015). Therefore, treatment with antiangiogenic drugs, including Ac-RLYE, that target the VEGF-A/VEGFR-2 axis is a useful regimen for promising outcomes by negatively regulating macrophage infiltration and polarization in preclinical and clinical settings (Dineen et al, 2008;Rivera and Bergers, 2015).…”