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 transdifferentiated 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Seftor EA,Brown KM,Chin L,Kirschmann DA,Wheaton WW,Protopopov A,Feng B,Balagurunathan Y,Trent JM,Nickoloff BJ,Seftor RE,Hendrix MJdoi
10.1158/0008-5472.CAN-05-2497subject
Has Abstractpub_date
2005-11-15 00:00:00pages
10164-9issue
22eissn
0008-5472issn
1538-7445pii
65/22/10164journal_volume
65pub_type
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