Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells

Ann Biomed Eng. 2021 Sep;49(9):2103-2113. doi: 10.1007/s10439-021-02727-w. Epub 2021 Feb 4.

Abstract

Conventional 2D cell culture, a traditional tool in pre-clinical studies, can hardly be regarded as a representation of a natural cell microenvironment. In this respect, it might result in altered cellular behaviors. To overcome such a limitation, different approaches have been tested to conduct more representative in vitro studies. In particular, the use of 3D cell culture introduces variables, such as cell-cell and cell-extracellular matrix interactions; cell features such as survival, proliferation and migration are consequently influenced. For an example, an enhanced drug resistance and increased invasiveness are shown by cancer cells when cultured in 3D versus 2D conventional culture models. In this setting however, non-uniform cell distribution and biological behaviors appear throughout the scaffold, due to reduced diffusion of oxygen and nutrients. Perfusion in bioreactor systems can be used to improve medium transport. In this line of reasoning, this study proposes a breast cancer cell culture model sustained by an integrated approach that couples a 3D environment and a fluid perfusion. This model improves viability and uniformness of cell distribution, while inducing morphological, functional and molecular cancer cell remodeling.

Keywords: 3D hydrogel scaffold; Cell distribution; Cell eccentricity; Cell migration; MDA-MB-231; Perfusion bioreactor systems; Rat tail collagen; Scratch wound healing assay.

MeSH terms

  • Bioreactors*
  • Breast Neoplasms
  • Cell Culture Techniques*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Collagen
  • Female
  • Gene Expression
  • Humans
  • Hydrogels
  • Matrix Metalloproteinases / genetics
  • Perfusion
  • Phenotype
  • Protein-Lysine 6-Oxidase / genetics
  • Vimentin / genetics
  • Wound Healing
  • rhoA GTP-Binding Protein

Substances

  • Hydrogels
  • VIM protein, human
  • Vimentin
  • RHOA protein, human
  • Collagen
  • LOX protein, human
  • Protein-Lysine 6-Oxidase
  • Matrix Metalloproteinases
  • rhoA GTP-Binding Protein