Combined MEK inhibition and tumor-associated macrophages depletion suppresses tumor growth in a triple-negative breast cancer mouse model.

Combined MEK inhibition and tumor-associated macrophages depletion suppresses tumor growth in a triple-negative breast cancer mouse model. Int Immunopharmacol. 2019 Aug 31;76:105864 Authors: Zhang Q, Le K, Xu M, Zhou J, Xiao Y, Yang W, Jiang Y, Xi Z, Huang T Abstract Tumor-associated macrophages (TAMs) are closely related to poor prognosis in triple-negative breast cancer (TNBC). Thus, gaining insight into how TAMs support cancer progression could contribute to effective therapies. We utilized the 4 T1 murine TNBC cell line and murine bone marrow-derived macrophages to assess TAM-mediated pro-proliferative effects in vivo and in vitro. Further, Transcriptional analysis was performed to identify pathways activated in TAM-stimulated 4 T1 cells. We also explored the therapeutic efficacy of combining a mitogen-activated protein kinase kinase (MEK) inhibitor with TAM-targeted therapy using a TNBC mouse model. We found that the presence of TAMs was significantly associated with proliferating cancer cells in a TNBC mouse model. Moreover, RNA sequencing analysis showed that TAMs could enhance mitogen-activated protein kinase (MAPK) pathway activation in 4 T1 cells compared to that in control cells. Further, the depletion of TAMs by clodronate liposomes significantly reduced MAPK pathway activation in vivo. In addition, the blockade of MAPK signaling by a MEK inhibitor repressed TAM-mediated cancer cell proliferation. Most importantly, ...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research