Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment

Elisabeth A. Seftor, Kevin M. Brown, Lynda Chin, Dawn A. Kirschmann, William W. Wheaton, Alexei Protopopov, Bin Feng, Yoganand Balagurunathan, Jeffrey M. Trent, Brian J. Nickoloff, Richard E.B. Seftor, Mary J.C. Hendrix

Research output: Contribution to journalArticle

Abstract

The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine whether these normal cells could be reprogrammed by inductive cues in the tumor cell microenvironment. The results show the epigenetic transdifferentiation of the normal melanocytic phenotype to that of an aggressive melanoma-like cell with commensurate increased migratory and invasive ability with no detectable genomic alterations. Removal of the trans-differentiated melanocytes from the inductive metastatic melanoma microenvironment results in a reversion to their normal phenotype. However, a normal melanocyte microenvironment had no epigenetic influence on the phenotype of metastatic melanoma cells. This novel approach identifies specific genes involved in the transdifferentiation of melanocytes to a more aggressive phenotype, which may offer significant therapeutic value.

Original languageEnglish (US)
Pages (from-to)10164-10169
Number of pages6
JournalCancer Research
Volume65
Issue number22
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Seftor, E. A., Brown, K. M., Chin, L., Kirschmann, D. A., Wheaton, W. W., Protopopov, A., Feng, B., Balagurunathan, Y., Trent, J. M., Nickoloff, B. J., Seftor, R. E. B., & Hendrix, M. J. C. (2005). Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment. Cancer Research, 65(22), 10164-10169. https://doi.org/10.1158/0008-5472.CAN-05-2497