MO Kim and SH Kim contributed equally to this work.
Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells
Article first published online: 16 AUG 2011
© 2011 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 24, Issue 5, pages 922–931, October 2011
How to Cite
Kim, M. O., Kim, S.-H., Oi, N., Lee, M. H., Yu, D. H., Kim, D. J., Cho, E. J., Bode, A. M., Cho, Y.-Y., Bowden, T. G. and Dong, Z. (2011), Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells. Pigment Cell & Melanoma Research, 24: 922–931. doi: 10.1111/j.1755-148X.2011.00891.x
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- Issue published online: 10 OCT 2011
- Article first published online: 16 AUG 2011
- Accepted manuscript online: 23 JUL 2011 09:36AM EST
- PUBLICATION DATA Received 10 September 2010, revised and accepted for publication 22 July 2011, published online 23 July 2011
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.