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Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress.
Hughes, Russell; Chen, Xinyue; Cowley, Natasha; Ottewell, Penelope D; Hawkins, Rhoda J; Hunter, Keith D; Hobbs, Jamie K; Brown, Nicola J; Holen, Ingunn.
Afiliación
  • Hughes R; Department of Oncology and Metabolism, University of Sheffield, and Experimental Cancer Medicine Centre, Sheffield S10 2RX, UK.
  • Chen X; Department of Oncology and Metabolism, University of Sheffield, and Experimental Cancer Medicine Centre, Sheffield S10 2RX, UK.
  • Cowley N; Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.
  • Ottewell PD; Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.
  • Hawkins RJ; Department of Oncology and Metabolism, University of Sheffield, and Experimental Cancer Medicine Centre, Sheffield S10 2RX, UK.
  • Hunter KD; Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.
  • Hobbs JK; School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
  • Brown NJ; Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.
  • Holen I; Department of Oncology and Metabolism, University of Sheffield, and Experimental Cancer Medicine Centre, Sheffield S10 2RX, UK.
Cancers (Basel) ; 13(6)2021 Mar 18.
Article en En | MEDLINE | ID: mdl-33803526
Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article Pais de publicación: Suiza