Publikationsdatum:
2010-07-03
Beschreibung:
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(-/-)gammac(-/-) 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(-/-)gammac(-/-) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898751/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898751/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boiko, Alexander D -- Razorenova, Olga V -- van de Rijn, Matt -- Swetter, Susan M -- Johnson, Denise L -- Ly, Daphne P -- Butler, Paris D -- Yang, George P -- Joshua, Benzion -- Kaplan, Michael J -- Longaker, Michael T -- Weissman, Irving L -- 1RC2 DE02077-01/DE/NIDCR NIH HHS/ -- F32 CA126252/CA/NCI NIH HHS/ -- F32 CA126252-03/CA/NCI NIH HHS/ -- UL1 RR025744/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Jul 1;466(7302):133-7. doi: 10.1038/nature09161.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, California 94304-5542, USA. aboiko@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20596026" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Antigens, Neoplasm/analysis/metabolism
;
Bone Transplantation
;
Bone and Bones/pathology
;
DNA-Binding Proteins/deficiency/genetics
;
Humans
;
Lung Neoplasms/secondary
;
Melanoma/*metabolism/*pathology
;
Melanoma-Specific Antigens
;
Mice
;
Mice, Knockout
;
Neoplasm Metastasis
;
Neoplasm Proteins/analysis/metabolism
;
Neoplasm Transplantation
;
Neoplastic Stem Cells/cytology/*metabolism/*pathology/transplantation
;
Nerve Tissue Proteins/deficiency/genetics/*metabolism
;
Neural Crest/cytology/*metabolism/pathology
;
Receptors, Nerve Growth Factor/deficiency/genetics/*metabolism
;
Skin/pathology
;
Skin Transplantation
;
Transplantation, Heterologous/pathology
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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