Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells

Myoung Ok Kim, Sung Hyun Kim, Naomi Oi, Mee Hyun Lee, Dong Hoon Yu, Dong Joon Kim, Eun Jin Cho, Ann M. Bode, Yong Yeon Cho, Tim G. Bowden, Zigang Dong

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The cancer microenvironment affects cancer cell proliferation and growth. Embryonic stem (ES)-preconditioned 3-dimensional (3-D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. However, the mechanism has not yet been clarified. Using the ES-preconditioned 3-D microenvironment model, we provide evidence showing that the ES microenvironment inhibits proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. We also found that the ES microenvironment suppresses telomerase activity and thereby induces senescence in SK-MEL-28 cells. Furthermore, we observed that gremlin, an antagonist of BMP4, is secreted from ES cells and plays an important role in cellular senescence. Knocking down gremlin in the ES microenvironment increases proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. Taken together, these results demonstrated that gremlin is a crucial factor responsible for abrogating melanoma properties in the ES-preconditioned 3-D microenvironment.

Original languageEnglish (US)
Pages (from-to)922-931
Number of pages10
JournalPigment Cell and Melanoma Research
Volume24
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Aging
  • Melanoma
  • Microenvironment
  • Senescence

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