Tumor-Associated Macrophages Suppress the Cytotoxic Activity of Antimitotic Agents.

ABSTRACT: Antimitotic agents, including Taxol, disrupt microtubule dynamics and cause a protracted mitotic arrest and subsequent cell death. Despite the broad utility of these drugs in breast cancer and other tumor types, clinical response remains variable. Tumor-associated macrophages (TAMs) suppress the duration of Taxol-induced mitotic arrest in breast cancer cells and promote earlier mitotic slippage. This correlates with a decrease in the phosphorylated form of histone H2AX (γH2AX), decreased p53 activation, and reduced cancer cell death in interphase. TAMs promote cancer cell viability following mitotic slippage in a manner sensitive to MAPK/ERK kinase (MEK) inhibition. Acute depletion of major histocompatibility complex class II low (MHCII^lo) TAMs increased Taxol-induced DNA damage

SUBMITTER: Olson OC 

PROVIDER: S-EPMC5614506 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature