Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling
| Autor: | Zhi Fen Wu, Steven G. Allen, Chelsea Fournier, Joel A. Yates, Ayse B. Hiziroglu, Euisik Yoon, Yu Chih Chen, Liwei Bao, Megan Altemus, Sofia D. Merajver, Julie M. Madden, Yu Heng Cheng |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microfluidics Biology Inflammatory breast cancer Article Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Movement Cell Line Tumor medicine Humans Clustered Regularly Interspaced Short Palindromic Repeats Phosphorylation skin and connective tissue diseases Lymph node Multidisciplinary Oncogene Chemotactic Factors Interleukin-6 Macrophages Interleukin-8 Cell migration Cell Differentiation Gene signature medicine.disease 3. Good health Interleukin-10 030104 developmental biology medicine.anatomical_structure rhoC GTP-Binding Protein 030220 oncology & carcinogenesis Culture Media Conditioned Cancer research Female Inflammatory Breast Neoplasms Mitogen-Activated Protein Kinases RhoC GTP-Binding Protein Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 tumor-extrinsic 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. |
| Databáze: | OpenAIRE |
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