Melanoma revives an embryonic migration program to promote plasticity and invasion

Pigment Cell Melanoma Res. 2012 Sep;25(5):573-83. doi: 10.1111/j.1755-148X.2012.01025.x. Epub 2012 Aug 2.

Abstract

Cancer cells must regulate plasticity and invasion to survive and metastasize. However, the identification of targetable mechanisms to inhibit metastasis has been slow. Signaling programs that drive stem and progenitor cells during normal development offer an inroad to discover mechanisms common to metastasis. Using a chick embryo transplant model, we have compared molecular signaling programs of melanoma and their embryonic progenitors, the neural crest. We report that malignant melanoma cells hijack portions of the embryonic neural crest invasion program. Genes associated with neural crest induction, delamination, and migration are dynamically regulated by melanoma cells exposed to an embryonic neural crest microenvironment. Specifically, we demonstrate that metastatic melanoma cells exploit neural crest-related receptor tyrosine kinases to increase plasticity and facilitate invasion while primary melanocytes may actively suppress these responses under the same microenvironmental conditions. We conclude that aberrant regulation of neural crest developmental genes promotes plasticity and invasiveness in malignant melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement*
  • Cellular Microenvironment / genetics
  • Chick Embryo
  • Disease Progression
  • Ephrins / genetics
  • Ephrins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanocytes / pathology
  • Melanoma / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Neural Crest / embryology*
  • Neural Crest / metabolism
  • Neural Crest / pathology*
  • Receptors, Eph Family / genetics
  • Receptors, Eph Family / metabolism
  • Signal Transduction / genetics

Substances

  • Ephrins
  • Receptors, Eph Family