BRAF Inhibition Stimulates Melanoma-Associated Macrophages to Drive Tumor Growth.

ABSTRACT:

Purpose

To investigate the roles of melanoma-associated macrophages in melanoma resistance to BRAF inhibitors (BRAFi).

Experimental design

An in vitro macrophage and melanoma cell coculture system was used to investigate whether macrophages play a role in melanoma resistance to BRAFi. The effects of macrophages in tumor resistance were examined by proliferation assay, cell death assay, and Western blot analyses. Furthermore, two mouse preclinical models were used to validate whether targeting macrophages can increase the antitumor activity of BRAFi. Finally, the number of macrophages in melanoma tissues was examined by immunohistochemistry.

Results

We demonstrate that in BRAF-mutant melanomas, BRAFi paradoxically activate the mitogen-activated protein kinase (MAPK) pa

SUBMITTER: Wang T 

PROVIDER: S-EPMC4383683 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature