Efficient tumor formation by single human melanoma cells

By E. Quintana, Mark Shackleton, M. Sabel, D. Fullen, T. Johnson, S. Morrison. Nature, 2008

1,692 citations recorded by the source corpus.

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.

Subfields: Genetics, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/8446d394e4a9e638653824734967f499af9bad02

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Citations in the corpus

Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. (2009, background): “For example, CD24 is a pan-epithelial marker in the mouse mammary gland, but not in human breast tissue where it serves exclusively as a luminal marker (Shackleton et al. 2006; Stingl et al. 2006; Raouf et al. 2008; Lim et al. 2009).”
Dynamic interplay between the collagen scaffold and tumor evolution (2010, background): “Interestingly, type I collagen and Matrigel (which contains BM constituents such as laminin-111 and type IV collagen) increase engraftment of cancer cells in mice [94-96].”
Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. (2012, positive): “Patient lung cancer cells were directly transplanted subcutaneously into NOD/SCID Il2rg / mice with Matrigel (Quintana et al., 2008).”
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment (2010, background): “This has in part been explained by immune responses observed in xenotransplantation assay”
Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways (2011, background): “Certain tumors, such as melanoma, exhibit high levels of CSCs suggesting that the hierarchical model may not apply for all tumors”
Cancer stem cells: current status and evolving complexities. (2012, background): “Furthermore, there is increased awareness that the nature of the xenotransplantation assay is critical for evaluating the existence of CSCs (Quintana et al., 2008).”
CLONAL EVOLUTION IN CANCER (2012, background): “The frequency of cancer stem cells could then increase from low to very high frequency as the disease progresse”
Epithelial-mesenchymal transitions in development and disease. (2009, background): “However, some studies suggest that tumors are not necessarily initiated by rare cancer stem cells and that a significant percentage of individual human melanoma cells can efficiently form tumors (Kelly et al., 2007; Quintana et al., 2008).”
AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective (2010, positive): “The recent publication by Quintana and colleagues showed that by optimizing xenotransplantation procedures, one can increase the frequency of tumor-initiating human melanoma cells (197).”
Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells (2009, positive): “However, brain tumor stem cells exhibit significant distinctions from normal stem cells in frequency, proliferation, aberrant expression of differentiation markers, chromosomal abnormalities, and tumor formation (Quintana et al., 2008; Reya et al., 2001; Vescovi et al., 2006).”
Hallmarks of cancer: the next generation. (2011, neutral): “Nevertheless, the importance of CSCs as a distinct phenotypic subclass of neoplastic cells remains a matter of debate, as does their oft-cited rarity within tumors (Boiko et al., 2010; Gupta et al., 2009; Quintana et al., 2008).”