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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number39190
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Dec 19

Fingerprint

Inflammatory Breast Neoplasms
GTP Phosphohydrolases
Macrophages
Conditioned Culture Medium
Breast Neoplasms
Lab-On-A-Chip Devices
Neoplasm Metastasis
Cell Line
Neoplasms
Chemotactic Factors
Interleukin-8
Oncogenes
Cell Movement
Interleukin-6
Breast
Lymph Nodes
Phenotype

All Science Journal Classification (ASJC) codes

  • General

Cite this

Allen, S. G., Chen, Y. C., Madden, J. M., Fournier, C. L., Altemus, M. A., Hiziroglu, A. B., ... Merajver, S. D. (2016). Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling. Scientific reports, 6, [39190]. https://doi.org/10.1038/srep39190
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. / Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling. In: Scientific reports. 2016 ; Vol. 6.
@article{c7cdef4efc284655ac2129c4e77e8759,
title = "Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling",
abstract = "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.",
author = "Allen, {Steven G.} and Chen, {Yu Chih} and Madden, {Julie M.} and Fournier, {Chelsea L.} and Altemus, {Megan A.} and Hiziroglu, {Ayse B.} and Cheng, {Yu Heng} and Wu, {Zhi Fen} and Liwei Bao and Yates, {Joel A.} and Euisik Yoon and Merajver, {Sofia D.}",
year = "2016",
month = "12",
day = "19",
doi = "10.1038/srep39190",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

Allen, SG, Chen, YC, Madden, JM, Fournier, CL, Altemus, MA, Hiziroglu, AB, Cheng, YH, Wu, ZF, Bao, L, Yates, JA, Yoon, E & Merajver, SD 2016, 'Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling', Scientific reports, vol. 6, 39190. https://doi.org/10.1038/srep39190

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

In: Scientific reports, Vol. 6, 39190, 19.12.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling

AU - Allen, Steven G.

AU - Chen, Yu Chih

AU - Madden, Julie M.

AU - Fournier, Chelsea L.

AU - Altemus, Megan A.

AU - Hiziroglu, Ayse B.

AU - Cheng, Yu Heng

AU - Wu, Zhi Fen

AU - Bao, Liwei

AU - Yates, Joel A.

AU - Yoon, Euisik

AU - Merajver, Sofia D.

PY - 2016/12/19

Y1 - 2016/12/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85006707333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006707333&partnerID=8YFLogxK

U2 - 10.1038/srep39190

DO - 10.1038/srep39190

M3 - Article

C2 - 27991524

AN - SCOPUS:85006707333

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 39190

ER -

Allen SG, Chen YC, Madden JM, Fournier CL, Altemus MA, Hiziroglu AB et al. Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling. Scientific reports. 2016 Dec 19;6. 39190. https://doi.org/10.1038/srep39190