Spheroid formation of human thyroid cancer cells under simulated microgravity: a possible role of CTGF and CAV1

Cell Commun Signal. 2014 May 10:12:32. doi: 10.1186/1478-811X-12-32.

Abstract

Background: Multicellular tumor spheroids (MCTS) formed scaffold-free under microgravity are of high interest for research and medicine. Their formation mechanism can be studied in space in real microgravity or on Earth using ground-based facilities (GBF), which simulate microgravity. On Earth, these experiments are more cost-efficient and easily performable. However, each GBF might exert device-specific and altered superimposingly gravity-dependent effects on the cells.

Results: FTC-133 human thyroid cancer cells were cultivated on a 2D clinostat (CN) and a random positioning machine (RPM) and compared with corresponding 1 g control cells. Harvested cell samples were investigated by microscopy, quantitative realtime-PCR and Multi-Analyte Profiling. Spheroid formation and growth occurred during 72 h of cultivation on both devices. Cytokine secretion and gene activation patterns frequently altered in different ways, when the cells were cultured either on the RPM or the CN. A decreased expression of CAV1 and CTGF in MCTS compared to adherent cells was observed after cultivation on both machines.

Conclusion: The development of MCTS proceeds similarly on the RPM and the CN resembling the situation observed under real microgravity conditions, while no MCTS formation was observed at 1 g under identical experimental conditions. Simultaneously, changes in the regulation of CTGF and CAV1 appeared in a comparable manner on both machines. A relationship between these molecules and MCTS formation is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Line, Tumor
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism*
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Weightlessness*

Substances

  • CAV1 protein, human
  • CCN2 protein, human
  • Caveolin 1
  • Cytokines
  • RNA, Messenger
  • Connective Tissue Growth Factor