title: Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks.
abstract: We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow-derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC-CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow-derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population.
authors.affiliation: Comprehensive Cancer Center and School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109, USA. sulingl@med.umich.edu
authors.forename: Suling
authors.initials: S
authors.lastname: Liu
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Sing J
authors.initials: SJ
authors.lastname: Ou
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Clouthier
authors.forename: Shivani H
authors.initials: SH
authors.lastname: Patel
authors.forename: Florence
authors.initials: F
authors.lastname: Monville
authors.forename: Hasan
authors.initials: H
authors.lastname: Korkaya
authors.forename: Amber
authors.initials: A
authors.lastname: Heath
authors.forename: Julie
authors.initials: J
authors.lastname: Dutcher
authors.forename: Celina G
authors.initials: CG
authors.lastname: Kleer
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dontu
authors.forename: Russell
authors.initials: R
authors.lastname: Taichman
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D016207:Cytokines; D000444:Aldehyde Dehydrogenase