title: Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells.
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.
authors.affiliation: School of Engineering and Sciences, Tecnologico de Monterrey, Campus Monterrey, Ave., Eugenio Garza Sada 2501 Sur, Monterrey, NL 64849, Mexico.
authors.forename: Hyundoo
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Center for Soft and Living Matter, Institute for Basic Science (IBS), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Changsik
authors.initials: C
authors.lastname: Shin
authors.affiliation: Center for Soft and Living Matter, Institute for Basic Science (IBS), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Park
authors.affiliation: School of Engineering and Sciences, Tecnologico de Monterrey, Campus Monterrey, Ave., Eugenio Garza Sada 2501 Sur, Monterrey, NL 64849, Mexico.|Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
authors.forename: Enoch
authors.initials: E
authors.lastname: Kang
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Bongseo
authors.initials: B
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Jae-A
authors.initials: JA
authors.lastname: Han
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Do
authors.affiliation: Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Chonan-Si Chungcheongnam-do 31538, Republic of Korea.
authors.forename: Seongho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Center for Soft and Living Matter, Institute for Basic Science (IBS), UNIST-gil 50, Ulsan 44919, Republic of Korea.|School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea.
authors.forename: Yoon-Kyoung
authors.initials: YK
authors.lastname: Cho
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D054415:Chemokine CCL19 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D061986:MCF-7 Cells; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C515460:CCL19 protein, human; D054415:Chemokine CCL19; D053583:Interleukin-1beta; D015850:Interleukin-6; D007371:Interferon-gamma