Human Melanoma Initiating Cells Express Neural Crest Nerve Growth Factor Receptor CD271

By A. D. Boiko, O. Razorenova, M. van de Rijn, S. Swetter, Denise L. Johnson, D. Ly, P. Butler, George P. Yang, Ben-zion Joshua, M. Kaplan and 2 more. Nature, 2010

762 citations recorded by the source corpus.

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−/−γc−/− 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−/−γc−/− 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.

Subfields: Immunology, Oncology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/597e434a2a1af93bd3617f9f6cc52382381b481e

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Citations in the corpus

Cancer stem cells: current status and evolving complexities. (2012, background): “…CSCs for some ovarian (Stewart et al., 2011) and breast cancer (Meyer et al., 2010) xenografts remained constant, the frequency of CSCs has been observed to increase during serial transplantation, thus emphasizing the need to study early-passage tumors (Boiko et al., 2010; Ishizawa et al., 2010).”
Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized (2010, methodology): “Our results with CD271 are different from the results reported by Boiko et al. (2010) even though both studies used the same anti-CD271 antibody, both studied a similar spectrum of melanoma stages (mainly stage III), and both studied a combination of xenografted tumors and tumors obtained directly…”
Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, neutral): “Some have suggested that melanomas have intrinsically different populations of tumorigenic and nontumorigenic cells that can be distinguished based on ABCB5 (Schatton et al., 2008) or CD271 (Civenni et al., 2011; Boiko et al., 2010) expression.”
Evolution of the cancer stem cell model. (2014, neutral): “As most tumor cells were T-IC, such tumors appear to be homogeneous and not following a hierarchical model of tumor organization, although some have argued that there may be methodological explanations (Boiko et al., 2010).”
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).”
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq (2016, neutral): “A second transcriptional program, negatively correlated with the MITF program and with PC4 and PC5 (Pearson correlation P<10−24), included AXL and NGFR (p75NTR), a marker of resistance to various targeted therapies (27, 28) and a putative melanoma cancer stem cell marker (29), respectively (Table S8”
Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. (2012, positive): “Recently it was proposed that at earlier stages of tumorigenesis, rare TIC clones differentiate into nonmalignant progeny to form the bulk of the tumor, whereas at advanced stages, TIC clones constitute the bulk of the tumor (Boiko et al., 2010).”