Amniotic membrane-derived cells inhibit proliferation of cancer cell lines by inducing cell cycle arrest

J Cell Mol Med. 2012 Sep;16(9):2208-18. doi: 10.1111/j.1582-4934.2012.01531.x.

Abstract

Cells derived from the amniotic foetal membrane of human term placenta have drawn particular attention mainly for their plasticity and immunological properties, which render them interesting for stem-cell research and cell-based therapeutic applications. In particular, we have previously demonstrated that amniotic mesenchymal tissue cells (AMTC) inhibit lymphocyte proliferation in vitro and suppress the generation and maturation of monocyte-derived dendritic cells. Here, we show that AMTC also significantly reduce the proliferation of cancer cell lines of haematopoietic and non-haematopoietic origin, in both cell-cell contact and transwell co-cultures, therefore suggesting the involvement of yet-unknown inhibitory soluble factor(s) in this 'cell growth restraint'. Importantly, we provide evidence that the anti-proliferative effect of AMTC is associated with induction of cell cycle arrest in G0/G1 phase. Gene expression analyses demonstrate that AMTC can down-regulate cancer cells' mRNA expression of genes associated with cell cycle progression, such as cyclins (cyclin D2, cyclin E1, cyclin H) and cyclin-dependent kinase (CDK4, CDK6 and CDK2), whilst they up-regulate cell cycle negative regulator such as p15 and p21, consistent with a block in G0/G1 phase with no progression to S phase. Taken together, these findings warrant further studies to investigate the applicability of these cells for controlling cancer cell proliferation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion / cytology*
  • Amnion / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Coculture Techniques
  • Cyclin D2 / genetics
  • Cyclin D2 / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin H / genetics
  • Cyclin H / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Down-Regulation
  • G1 Phase / drug effects
  • HeLa Cells
  • Humans
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • U937 Cells
  • Up-Regulation

Substances

  • CCND2 protein, human
  • CCNE1 protein, human
  • Cyclin D2
  • Cyclin E
  • Cyclin H
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p21
  • Oncogene Proteins
  • RNA, Messenger
  • CDK2 protein, human
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6