Substrate stiffness regulated migration and angiogenesis potential of A549 cells and HUVECs

J Cell Physiol. 2018 Apr;233(4):3407-3417. doi: 10.1002/jcp.26189. Epub 2017 Oct 27.

Abstract

Tumor tissue tends to stiffen during solid tumor progression. Substrate stiffness is known to alter cell behaviors, such as proliferation and migration, during which angiogenesis is requisite. Mono- and co-culture systems of lung cancer cell line A549 and human umbilical vein endothelial cells (HUVECs), on polydimethylsiloxane substrates (PDMS) with varying stiffness, were used for investigating the effects of substrate stiffness on the migration and angiogenesis of lung cancer. The expressions of matrix metalloproteinases (MMPs) and angiogenesis-related growth factors were up-regulated with the increase of substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase (TIMPs) were down-regulated with increasing substrate stiffness. Our data not only suggested that stiff substrate may promote the migration and angiogenesis capacities of lung cancer, but also suggested that therapeutically targeting lung tumor stiffness or response of ECs to lung tumor stiffness may help reduce migration and angiogenesis of lung tumor.

Keywords: angiogenesis; migration; proliferation; stiffness; tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Neovascularization, Pathologic / metabolism*
  • Up-Regulation
  • Vascular Stiffness / physiology*

Substances

  • Matrix Metalloproteinases