Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized

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

doi:10.1016/j.ccr.2010.10.012

Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized

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

Research output: Contribution to journal › Article › peer-review

482 Scopus citations

Abstract

We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and nontumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We found 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγ^null mice. All stage II, III, and IV melanomas obtained directly from patients had common tumorigenic cells. All tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation. We were unable to find any large subpopulation of melanoma cells that lacked tumorigenic potential. None of 22 heterogeneously expressed markers, including CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice, irrespective of whether they arose from CD271^- or CD271⁺ cells. Many markers appeared to be reversibly expressed by tumorigenic melanoma cells.

Original language	English (US)
Pages (from-to)	510-523
Number of pages	14
Journal	Cancer Cell
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2010.10.012
State	Published - Nov 16 2010

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccr.2010.10.012

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@article{e1cb7b96fa7f4594a601aefad068a273,

title = "Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized",

abstract = "We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and nontumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We found 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγnull mice. All stage II, III, and IV melanomas obtained directly from patients had common tumorigenic cells. All tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation. We were unable to find any large subpopulation of melanoma cells that lacked tumorigenic potential. None of 22 heterogeneously expressed markers, including CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice, irrespective of whether they arose from CD271- or CD271+ cells. Many markers appeared to be reversibly expressed by tumorigenic melanoma cells.",

author = "Elsa Quintana and Mark Shackleton and Foster, {Hannah R.} and Fullen, {Douglas R.} and Sabel, {Michael S.} and Johnson, {Timothy M.} and Morrison, {Sean J.}",

note = "Funding Information: This work was supported by the Howard Hughes Medical Institute and by the Allen H. Blondy Research Fellowship. The University of Michigan (UM) Melanoma Bank was supported by a gift from Lewis and Lillian Becker. Flow cytometry was partially supported by UM-Comprehensive Cancer NIH CA46592. Thanks to David Adams and the UM Core Facility for flow cytometry, to Melissa Voutsalath for tissue collection, and to Daniel Weinberg for technical assistance. Elsa Quintana was supported by the Marie Curie Outgoing International Fellowship from the European Commission. Mark Shackleton was supported by the Australian National Heath and Medical Research Council, the Human Frontiers Science Program, and Australia Post. ",

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doi = "10.1016/j.ccr.2010.10.012",

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AU - Sabel, Michael S.

AU - Johnson, Timothy M.

AU - Morrison, Sean J.

N1 - Funding Information: This work was supported by the Howard Hughes Medical Institute and by the Allen H. Blondy Research Fellowship. The University of Michigan (UM) Melanoma Bank was supported by a gift from Lewis and Lillian Becker. Flow cytometry was partially supported by UM-Comprehensive Cancer NIH CA46592. Thanks to David Adams and the UM Core Facility for flow cytometry, to Melissa Voutsalath for tissue collection, and to Daniel Weinberg for technical assistance. Elsa Quintana was supported by the Marie Curie Outgoing International Fellowship from the European Commission. Mark Shackleton was supported by the Australian National Heath and Medical Research Council, the Human Frontiers Science Program, and Australia Post.

PY - 2010/11/16

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N2 - We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and nontumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We found 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγnull mice. All stage II, III, and IV melanomas obtained directly from patients had common tumorigenic cells. All tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation. We were unable to find any large subpopulation of melanoma cells that lacked tumorigenic potential. None of 22 heterogeneously expressed markers, including CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice, irrespective of whether they arose from CD271- or CD271+ cells. Many markers appeared to be reversibly expressed by tumorigenic melanoma cells.

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Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized

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