title: Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells.
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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Naomi
authors.initials: N
authors.lastname: Oi
authors.forename: Mee Hyun
authors.initials: MH
authors.lastname: Lee
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Cho
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Tim G
authors.initials: TG
authors.lastname: Bowden
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D016922:Cellular Senescence; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins