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Cho, Yoon-Kyoung
FRUITS Lab.
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Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells

Author(s)
Hwang, Hyun-dooShin, ChangsikPark, JuheeKang, EnochChoi, Bang-seoHan, Jae-ADo, YoonkyungRyu, Seong-hoCho, Yoon-Kyoung
Issued Date
2016-07
DOI
10.1038/srep30207
URI
https://scholarworks.unist.ac.kr/handle/201301/20198
Fulltext
http://www.nature.com/articles/srep30207
Citation
SCIENTIFIC REPORTS, v.6, pp.30207
Abstract
Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1β and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1β, IL-6 and IFN-γ. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.
Publisher
NATURE PUBLISHING GROUP
ISSN
2045-2322
Keyword
EXPRESSIONINFILTRATIONMETASTASISN-TERMINAL KINASETUMOR PROGRESSIONIMMUNE-SYSTEMINFLAMMATIONMIGRATIONMICROENVIRONMENTACTIVATION

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