Short-Term Microgravity Influences Cell Adhesion in Human Breast Cancer Cells

Int J Mol Sci. 2019 Nov 15;20(22):5730. doi: 10.3390/ijms20225730.

Abstract

With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator random positioning machine (iRPM)), hypergravity (hyper-g), and vibration (VIB) on triple-negative breast cancer (TNBC) cells (MDA-MB-231 cell line) with the aim to study early changes in the gene expression of factors associated with cell adhesion, apoptosis, nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. We had the opportunity to attend a parabolic flight (PF) mission and to study changes in RNA transcription in the MDA-MB cells exposed to PF maneuvers (29th Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). PF maneuvers induced an early up-regulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1) and a delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31). ICAM-1, VCAM-1 and CD44 protein levels were elevated, whereas the NF-κB subunit p-65 and annexin-A2 protein levels were reduced after the 31st parabola (P31). The PRKCA, RAF1, BAX mRNA were not changed and cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers. Hyper-g-exposure of the cells elevated the expression of CD44 and NFKBIA mRNAs, iRPM-exposure downregulated ANXA2 and BAX, whereas VIB did not affect the TNBC cells. The early changes in ICAM-1 and VCAM-1 and the rapid decrease in the NF-κB subunit p-65 might be considered as fast-reacting, gravity-regulated and cell-protective mechanisms of TNBC cells exposed to altered gravity conditions. This data suggest a key role for the detected gravity-signaling elements in three-dimensional growth and metastasis.

Keywords: NF-κB; apoptosis; breast cancer cells; cell adhesion; hypergravity; microgravity.

MeSH terms

  • Apoptosis / physiology
  • Breast Neoplasms / metabolism*
  • Cell Adhesion / physiology*
  • Cell Line, Tumor
  • Humans
  • Hyaluronan Receptors / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Protein Kinase C-alpha / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Weightlessness Simulation
  • Weightlessness*

Substances

  • Hyaluronan Receptors
  • NF-kappa B
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, human
  • PRKCA protein, human
  • Protein Kinase C-alpha
  • Mitogen-Activated Protein Kinases