Intravital microscopy of collective invasion plasticity in breast cancer

Dis Model Mech. 2018 Aug 23;11(9):dmm034330. doi: 10.1242/dmm.034330.

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 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.

Keywords: Actin dynamics; Carcinoma invasion; Intravital microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Plasticity*
  • Cell Proliferation
  • Female
  • HEK293 Cells
  • Humans
  • Imaging, Three-Dimensional
  • Intravital Microscopy*
  • Mammary Neoplasms, Animal / blood supply
  • Mammary Neoplasms, Animal / diagnostic imaging*
  • Mammary Neoplasms, Animal / pathology*
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / pathology
  • Stromal Cells / pathology

Substances

  • Actins