title: Human Umbilical Cord Mesenchymal Stem Cells Promote Breast Cancer Metastasis by Interleukin-8- and Interleukin-6-Dependent Induction of CD44(+)/CD24(-) Cells.
abstract: Although emerging evidence links mesenchymal stem cells (MSCs) with cancer metastasis, the underlying mechanisms are poorly understood. In the present study, we found that human umbilical cord-derived MSCs (UC-MSCs) promoted MCF-7 cell migration in vitro and metastasis in vivo. To explore the mechanisms, the characteristics of MCF-7 cells cocultured with UC-MSCs were assessed. The expression and secretion of interleukin-8 (IL-8) and IL-6 were induced in MCF-7 cells cocultured with UC-MSCs. However, neutralization of IL-8 or IL-6 secreted by UC-MSCs could attenuate the enhanced expression of IL-8 and IL-6 in MCF-7 cells cocultured with UC-MSCs, which subsequently alleviated the enhanced migration. Similar to UC-MSCs, exogenous human recombinant IL-8 or IL-6 also promoted IL-8 and IL-6 expression and MCF-7 cell migration. In addition to enhanced IL-8 and IL-6 expression, MCF-7 cells cocultured with UC-MSCs displayed enhanced mammosphere-forming ability and increased percentage of CD44(+)/CD24(-) cells. However, epithelial-to-mesenchymal transition (EMT) was not observed in MCF-7 cells cocultured with UC-MSCs. Taken together, these results suggested that IL-8 and IL-6 secreted by UC-MSCs activated the autocrine IL-8 and IL-6 signaling in MCF-7 cells and induced CD44(+)/CD24(-) cells, which subsequently promoted MCF-7 cell migration in vitro and metastasis in vivo.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Ma
authors.forename: Dandan
authors.initials: D
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Chi
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Han
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Feng
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; C508606:CXCL8 protein, human; D018960:Hyaluronan Receptors; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins