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

By E. Quintana, Mark Shackleton, Hannah R. Foster, D. Fullen, M. Sabel, T. Johnson, S. Morrison. Cancer Cell, 2010

621 citations recorded by the source corpus.

Summary We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and non-tumorigenic 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 upon 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. Significance In cancers that follow a stem cell model, phenotypically distinct tumorigenic cells form abundant and phenotypically diverse non-tumorigenic progeny in a hierarchical manner that resembles normal stem cell differentiation. In contrast to this model, our results indicate that primary cutaneous or metastatic melanomas from patients have common and phenotypically diverse tumorigenic cells that undergo reversible phenotypic changes in vivo. Most of the phenotypic heterogeneity in melanoma is therefore not associated with a loss of tumorigenic potential or organized in stable hierarchies. These data suggest a phenotypic plasticity model in which phenotypic heterogeneity is driven largely by reversible changes within lineages of tumorigenic cells rather than by irreversible epigenetic or genetic changes.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/c268ffcfebe92d7053beb2b3f606e845eb40e370

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Citations in the corpus

Cancer stem cells: current status and evolving complexities. (2012, background): “Finally, the perturbation of other stromal mesenchymal cells such as osteoprogenitors candisrupt homeostasis, resulting inmyelodysplasia and secondary leukemia (Raaijmakers et al., 2010).”
Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. (2012, positive): “Although the validity of the CSC model is an issue of controversy in melanoma (Quintana et al., 2008, 2010; Boiko et al., 2010; Civenni et al., 2011), many other solid tumors appear to follow the CSC model (Ishizawa et al., 2010).”
Targeting cancer stem cell pathways for cancer therapy (2020, background): “Breast CSCs have different expression patterns of surface biomarkers, such as CD44, CD24, SP, and ALDH CD271 or CD271 melanoma stem cells can form tumors in SCID mice.(40) The heterogeneity of CSCs has also been found in other cancers, including glioblastoma,(41) prostate cancer,(42) and lung cancer”
Evolution of the cancer stem cell model. (2014, background): “Through the use of recipients with increased immune-deﬁciency, the assayed frequency of T-IC in melanoma changed by many orders of magnitude such that the most permissive recipient read out a T-IC frequency of virtually 1 in 1 (Quintana et al., 2010).”
Mechanisms of chemoresistance in cancer stem cells (2013, background): “While it is now clear that not all heterogenous cancers follow the hierarchical model [6], there is growing evidence for a role of CSCs in a number of cancers.”
Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, background): “We also identified 20 other markers that are heterogeneously expressed by human melanoma cells and transplanted just 10 cells that were either positive or negative for each of these markers into NOD/SCID IL2Rgnull mice (Quintana et al., 2010).”