The hypoxic tumor microenvironment in vivo selects the cancer stem cell fate of breast cancer cells.
Background: Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate...
| Publicado en: | Breast Cancer Research Vol. 20; pp. 1 - 2 |
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| Autores principales: | , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
3/6/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=128324162&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 128324162 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 3/6/2018 vid: 20 pid: 24147 pub: BioMed Central artinfo: ui: 128324162 128324162 NLM29510720 128324162 10.1186/s13058-018-0944-8 NLM29510720 128324162 ppf: 1 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: The hypoxic tumor microenvironment in vivo selects the cancer stem cell fate of breast cancer cells. aug: au: Kim, Hoon Lin, Qun Glazer, Peter M. Yun, Zhong affil: Department of Therapeutic RadiologyYale University School of MedicineP. O. Box 20804006520-8040New HavenCTUSA sug: subj: Cell Physiology Breast Neoplasms Stem Cells Metabolism Animal Studies Cell Differentiation Stem Cells Pathology Breast Neoplasms Pathology Mice Female Cell Line, Tumor Human Validation Studies Comparative Studies Evaluation Research Multicenter Studies Female ab: Background: Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo by the hypoxic tumor microenvironment (TME).Methods: We established a hypoxia-sensing xenograft model to identify hypoxic tumor cell in vivo primarily using human breast cancer cell lines MDA-MB-231 and MCF7. Hypoxic tumor cells were identified in situ by fluorescence of green fluorescence protein. They were further isolated from xenografts, purified and sorted by flow cytometry for detailed analysis of their stem cell characteristics.Results: We have found that hypoxic tumor cells freshly isolated from xenografts contain increased subpopulations of tumor cells with cancer stem cell (CSC)-like characteristics. The CSC characteristics of the hypoxic tumor cells are further enhanced upon re-implantation in vivo, whereas secondary xenografts derived from the non-hypoxic tumor cells remain similar to the primary xenografts. Interestingly, the phenotypes exhibited by the hypoxic tumor cells are stable and remain distinctively different from those of the non-hypoxic tumor cells isolated from the same tumor mass even when they are maintained under the same ambient culture conditions. Mechanistically, the PI3K/AKT pathway is strongly potentiated in the hypoxic tumor cells and is required to maintain the CSC-like phenotype. Importantly, the differential cell fates between hypoxic and non-hypoxic tumor cells are only found in tumor cells isolated from the hypoxic TME in vivo and are not seen in tumor cells treated by hypoxia in vitro alone.Conclusions: These previously unknown observations suggest that the hypoxic TME may promote malignant progression and therapy resistance by coordinating induction, selection and/or preferential maintenance of the CSC-like phenotype in tumor cells. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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