title: Cancer Stem Cells Protect Non-Stem Cells From Anoikis: Bystander Effects.
abstract: Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non-stem cells is crucial for developing a novel cancer therapy. We used CSC-like and non-stem breast cancer MDA-MB-231 and MDA-MB-453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E-cadherin)-extracellular signal-regulated kinase (Erk) axis in anoikis. Data from E-cadherin small hairpin RNA assay and mitogen-activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E-cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC-like cells, increased secretion of interleukin-6 (IL-6) and growth-related oncogene (Gro) chemokines was detected during mammosphere culture in non-stem cells. Similar results were observed in mixed cells. Interestingly, CSC-like cells protected non-stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC-like cells and non-stem cells. J. Cell. Biochem. 117: 2289-2301, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: Seog-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: Per H
authors.initials: PH
authors.lastname: Basse
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.affiliation: Protein Metabolism Medical Research Center and Department of Biomedical Science, College of Medicine, Seoul National University, Seoul, 110-799, Korea.
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Kwon
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.|Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors.forename: Yong J
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D015703:Antigens, CD; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D024201:Bystander Effect; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins
keywords: ANOIKIS; BYSTANDER EFFECT; CANCER STEM-LIKE CELLS; ERK; NON-STEM CELLS