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Competitive interactions of cancer cells and normal cells via secretory microRNAs

Nobuyoshi Kosaka1, Haruhisa Iguchi, Yusuke Yoshioka

  • 1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

The Journal of Biological Chemistry
|November 30, 2011
PubMed

Insights

Normal cells secrete tumor-suppressive microRNAs (miRNAs) that inhibit cancer cell growth. Secreted miR-143 specifically reduced proliferation of prostate cancer cells, revealing a novel cell competition mechanism in tumor initiation.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Cancer research

Background:

  • Normal epithelial cells maintain tissue homeostasis through cell competition.
  • Dysregulation of cell competition is implicated in tumor initiation.
  • Secreted factors from normal cells can influence neighboring cell behavior.

Purpose of the Study:

  • To identify secreted tumor-suppressive molecules from normal epithelial cells.
  • To investigate the role of microRNAs (miRNAs) in cell competition and tumor suppression.
  • To determine if specific miRNAs can inhibit cancer cell proliferation.

Main Methods:

  • Analysis of miRNA expression in normal prostate epithelial cells (PNT-2) and prostate cancer cells (PC-3M-luc).
  • Treatment of cancer cells with culture supernatant from normal cells.
  • Global miRNA profiling of secreted factors.
  • In vitro and in vivo experiments to assess the effect of specific miRNAs on cancer cell growth.

Main Results:

  • Culture supernatant from normal PNT-2 cells inhibited proliferation of PC-3M-luc cancer cells.
  • A variety of tumor-suppressive miRNAs were identified in the secreted fraction of PNT-2 cells.
  • Secreted miR-143 demonstrated specific anti-proliferative effects on cancer cells both in vitro and in vivo.

Conclusions:

  • Secreted tumor-suppressive miRNAs act as anti-proliferative signals in cell competition.
  • miR-143 is a key secreted miRNA involved in inhibiting cancer cell growth.
  • This study offers a new perspective on tumor initiation mechanisms involving cell competition and secreted miRNAs.

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