Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271

Alexander D. Boiko, Olga V. Razorenova, Matt Van De Rijn, Susan M. Swetter, Denise L. Johnson, Daphne P. Ly, Paris D. Butler, George P. Yang, Benzion Joshua, Michael J. Kaplan, Michael T. Longaker, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

592 Scopus citations

Abstract

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271+ MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B-and natural-killer-deficient Rag2 -/- γc -/- mice. The CD271+ subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271+ melanoma cells into engrafted human skin or bone in Rag2 -/- γc -/- mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271- cells. We also show that in mice, tumours derived from transplanted human CD271+ melanoma cells were capable of metastatsis in vivo. CD271+ melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalNature
Volume466
Issue number7302
DOIs
StatePublished - 1 Jul 2010
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271'. Together they form a unique fingerprint.

Cite this