期刊
DISEASE MODELS & MECHANISMS
卷 11, 期 9, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.034330
关键词
Carcinoma invasion; Intravital microscopy; Actin dynamics
资金
- Nederlandse Organisatie voor Wetenschappelijk [NWO-VICI 918.11.626]
- FP7 Ideas: European Research Council [617430-DEEPINSIGHT]
- National Cancer Institute [U54 CA210184-01]
- Cancer Genomics Center
- Air Force Office of Scientific Research [FA9550-16-1-0052]
- National Institutes of Health [U01GM109887]
Cancer invasion programs are adaptive by switching between metastatic collective and single-cell dissemination; however, current intravital microscopy models for epithelial cancer in mice fail to reliably recreate such invasion plasticity. Using microimplantation of breast cancer spheroids into the murine mammary fat pad and live-cell monitoring, we show microenvironmental conditions and cytoskeletal adaptation during collective to single-cell transition in vivo. E-cadherin-expressing 4T1 and E-cadherin-negative MMT tumors both initiated collective invasion along stromal structures, reflecting invasion patterns in 3D organotypic culture and human primary ductal and lobular carcinoma. Collectively invading cells developed weakly oscillatory actin dynamics, yet provided zones for single-cell transitions with accentuated, more chaotic actin fluctuations. This identifies collective invasion in vivo as a dynamic niche and efficient source for single-cell release.
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