Intravital microscopy of collective invasion plasticity in breast cancer
Abstract
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 image-guided 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2018
- Source ID
- 10.1242/dmm.034330
Entities
People
- Chenlu Wang
- Leonard Campanello
- Manon Vullings
- Olga Ilina
- Pavel G. Gritsenko
- Peter Bult
- Peter Friedl
- Wolfgang Losert
Organizations
- Air Force Office of Scientific Research
- Dutch Research Council
- FP7 Ideas: European Research Council
- National Institutes of Health
- Radboud University Medical Centre
- University Medical Center Utrecht
- University of Maryland
- University of Texas at Austin