Efficient tumour formation by single human melanoma cells

Elsa Quintana, Mark Shackleton, Michael S. Sabel, Douglas R. Fullen, Timothy M. Johnson, Sean J. Morrison

Research output: Contribution to journalArticle

1352 Scopus citations

Abstract

A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1-0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg-/-) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.

Original languageEnglish (US)
Pages (from-to)593-598
Number of pages6
JournalNature
Volume456
Issue number7222
DOIs
StatePublished - Dec 4 2008

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Efficient tumour formation by single human melanoma cells'. Together they form a unique fingerprint.

  • Cite this

    Quintana, E., Shackleton, M., Sabel, M. S., Fullen, D. R., Johnson, T. M., & Morrison, S. J. (2008). Efficient tumour formation by single human melanoma cells. Nature, 456(7222), 593-598. https://doi.org/10.1038/nature07567