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

作者：Kim Myoung Ok; Kim Sung Hyun; Oi Naomi; Lee Mee Hyun; Yu Dong Hoon; Kim Dong Joon; Cho Eun Jin; Bode Ann M; Cho Yong Yeon; Bowden Tim G; Dong Zigang^*

来源：Pigment Cell & Melanoma Research, 2011, 24(5): 922-931.

DOI：10.1111/j.1755-148X.2011.00891.x

• microenvironment
• melanoma
• senescence
• aging

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.

• 出版日期2011-10