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

1311 Citations (Scopus)

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

Fingerprint

Melanoma
Severe Combined Immunodeficiency
Neoplasms
Heterologous Transplantation
Interleukin Receptor Common gamma Subunit
Wiskott-Aldrich Syndrome
Transplants

ASJC Scopus subject areas

  • General

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

Efficient tumour formation by single human melanoma cells. / Quintana, Elsa; Shackleton, Mark; Sabel, Michael S.; Fullen, Douglas R.; Johnson, Timothy M.; Morrison, Sean J.

In: Nature, Vol. 456, No. 7222, 04.12.2008, p. 593-598.

Research output: Contribution to journalArticle

Quintana, E, Shackleton, M, Sabel, MS, Fullen, DR, Johnson, TM & Morrison, SJ 2008, 'Efficient tumour formation by single human melanoma cells', Nature, vol. 456, no. 7222, pp. 593-598. https://doi.org/10.1038/nature07567
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008 Dec 4;456(7222):593-598. https://doi.org/10.1038/nature07567
Quintana, Elsa ; Shackleton, Mark ; Sabel, Michael S. ; Fullen, Douglas R. ; Johnson, Timothy M. ; Morrison, Sean J. / Efficient tumour formation by single human melanoma cells. In: Nature. 2008 ; Vol. 456, No. 7222. pp. 593-598.
@article{191a6bfebeeb4bd98881ee614e2fc403,
title = "Efficient tumour formation by single human melanoma cells",
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.",
author = "Elsa Quintana and Mark Shackleton and Sabel, {Michael S.} and Fullen, {Douglas R.} and Johnson, {Timothy M.} and Morrison, {Sean J.}",
year = "2008",
month = "12",
day = "4",
doi = "10.1038/nature07567",
language = "English (US)",
volume = "456",
pages = "593--598",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7222",

}

TY - JOUR

T1 - Efficient tumour formation by single human melanoma cells

AU - Quintana, Elsa

AU - Shackleton, Mark

AU - Sabel, Michael S.

AU - Fullen, Douglas R.

AU - Johnson, Timothy M.

AU - Morrison, Sean J.

PY - 2008/12/4

Y1 - 2008/12/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=57349143739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57349143739&partnerID=8YFLogxK

U2 - 10.1038/nature07567

DO - 10.1038/nature07567

M3 - Article

VL - 456

SP - 593

EP - 598

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7222

ER -