The melanocyte differentiation program predisposes to metastasis after neoplastic transformation

Piyush B. Gupta, Charlotte Kuperwasser, Jean Philippe Brunet, Sridhar Ramaswamy, Wen Lin Kuo, Joe Gray, Stephen P. Naber, Robert A. Weinberg

Research output: Contribution to journalArticle

315 Citations (Scopus)

Abstract

The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression.

Original languageEnglish (US)
Pages (from-to)1047-1054
Number of pages8
JournalNature Genetics
Volume37
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Melanocytes
Melanoma
Neoplasm Metastasis
Neural Crest
Gastropoda
Cell Movement
Genes
Nevus
Microarray Analysis
Fibroblasts
Epithelial Cells
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gupta, P. B., Kuperwasser, C., Brunet, J. P., Ramaswamy, S., Kuo, W. L., Gray, J., ... Weinberg, R. A. (2005). The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nature Genetics, 37(10), 1047-1054. https://doi.org/10.1038/ng1634

The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. / Gupta, Piyush B.; Kuperwasser, Charlotte; Brunet, Jean Philippe; Ramaswamy, Sridhar; Kuo, Wen Lin; Gray, Joe; Naber, Stephen P.; Weinberg, Robert A.

In: Nature Genetics, Vol. 37, No. 10, 10.2005, p. 1047-1054.

Research output: Contribution to journalArticle

Gupta, PB, Kuperwasser, C, Brunet, JP, Ramaswamy, S, Kuo, WL, Gray, J, Naber, SP & Weinberg, RA 2005, 'The melanocyte differentiation program predisposes to metastasis after neoplastic transformation', Nature Genetics, vol. 37, no. 10, pp. 1047-1054. https://doi.org/10.1038/ng1634
Gupta, Piyush B. ; Kuperwasser, Charlotte ; Brunet, Jean Philippe ; Ramaswamy, Sridhar ; Kuo, Wen Lin ; Gray, Joe ; Naber, Stephen P. ; Weinberg, Robert A. / The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. In: Nature Genetics. 2005 ; Vol. 37, No. 10. pp. 1047-1054.
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