Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling

作者：Allen Steven G; Chen Yu Chih; Madden Julie M; Fournier Chelsea L; Altemus Megan A; Hiziroglu Ayse B; Cheng Yu Heng; Wu Zhi Fen; Bao Liwei; Yates Joel A; Yoon Euisik; Merajver Sofia D

来源：Scientific Reports, 2016, 6(1): 39190.

DOI：10.1038/srep39190

Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC). Genetic profiling studies have been conducted to differentiate IBC from nIBC, but no IBC cancer-cell-specific gene signature has been identified. We hypothesized that a tumorextrinsic factor, notably tumor-associated macrophages, promotes and contributes to IBC's extreme metastatic phenotype. To this end, we studied the effect of macrophage-conditioned media (MCM) on IBC. We show that two IBC cell lines are hyper-responsive to MCM as compared to normal-like breast and aggressive nIBC cell lines. We further interrogated IBC's hyper-responsiveness to MCM using a microfluidic migration device, which permits individual cell migration path tracing. We found the MCM "primes" the IBC cells' cellular machinery to become extremely migratory in response to a chemoattractant. We determined that interleukins -6, -8, and -10 within the MCM are sufficient to stimulate this enhanced IBC migration effect, and that the known metastatic oncogene, RhoC GTPase, is necessary for the enhanced migration response.

• 出版日期2016-12-19