Cellular communication promotes mammosphere growth and collective invasion through microtubule‑like structures and angiogenesis

Oncol Rep. 2018 Dec;40(6):3297-3312. doi: 10.3892/or.2018.6778. Epub 2018 Oct 9.

Abstract

Networks of nanotubes and microtubules are highly valued in cellular communication, and collective cancer movement has been revealed to be associated with cell information exchange. In the present study, cellular communication was demonstrated to participate in mammosphere growth, differentiation and collective invasion. By promoting differentiation, networks of cells and microtubule‑like structures were verified. Analyses of cell cycle progression, stemness markers and gene expression indicated that mammospheres had collective characteristics of stemness and differentiation. Invasion assays revealed that networks of microtubule‑like structures promoted collective invasion. Conversely, using anti‑angiogenic intervention, the growth of stem‑like mammospheres and cellular communication links were effectively inhibited. In vivo experiments revealed that cellular communication promoted tumor growth and metastasis through the formation of nodular fusion, cluttered microtubule‑like structures and cancer stem cells, as well as vascular niches. In conclusion, the present results demonstrated that a network of cells and structures were largely present in mammosphere cellular communication in vitro and in vivo. Therefore, blocking cellular communication may prove beneficial in halting the progression of mammary tumors.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Communication / physiology*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Microtubules / drug effects
  • Microtubules / pathology*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology*
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / pathology*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab