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Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles

Cutaneous melanoma circulating tumour cells (CTCs) are phenotypically and molecularly heterogeneous. We profiled the gene expression of CTC subpopulations immunomagnetic-captured by targeting either the melanoma-associated marker, MCSP, or the melanoma-initiating marker, ABCB5. Firstly, the expressi...

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Autores principales: Aya-Bonilla, Carlos, Gray, Elin S., Manikandan, Jayapal, Freeman, James B., Zaenker, Pauline, Reid, Anna L., Khattak, Muhammad A., Frank, Markus H., Millward, Michael, Ziman, Mel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406574/
https://www.ncbi.nlm.nih.gov/pubmed/30769764
http://dx.doi.org/10.3390/cancers11020157
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author Aya-Bonilla, Carlos
Gray, Elin S.
Manikandan, Jayapal
Freeman, James B.
Zaenker, Pauline
Reid, Anna L.
Khattak, Muhammad A.
Frank, Markus H.
Millward, Michael
Ziman, Mel
author_facet Aya-Bonilla, Carlos
Gray, Elin S.
Manikandan, Jayapal
Freeman, James B.
Zaenker, Pauline
Reid, Anna L.
Khattak, Muhammad A.
Frank, Markus H.
Millward, Michael
Ziman, Mel
author_sort Aya-Bonilla, Carlos
collection PubMed
description Cutaneous melanoma circulating tumour cells (CTCs) are phenotypically and molecularly heterogeneous. We profiled the gene expression of CTC subpopulations immunomagnetic-captured by targeting either the melanoma-associated marker, MCSP, or the melanoma-initiating marker, ABCB5. Firstly, the expression of a subset of melanoma genes was investigated by RT-PCR in MCSP-enriched and ABCB5-enriched CTCs isolated from a total of 59 blood draws from 39 melanoma cases. Of these, 6 MCSP- and 6 ABCB5-enriched CTC fractions were further analysed using a genome-wide gene expression microarray. The transcriptional programs of both CTC subtypes included cell survival maintenance, cell proliferation, and migration pathways. ABCB5-enriched CTCs were specifically characterised by up-regulation of genes involved in epithelial to mesenchymal transition (EMT), suggesting an invasive phenotype. These findings underscore the presence of at least two distinct melanoma CTC subpopulations with distinct transcriptional programs, which may have distinct roles in disease progression and response to therapy.
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spelling pubmed-64065742019-03-21 Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles Aya-Bonilla, Carlos Gray, Elin S. Manikandan, Jayapal Freeman, James B. Zaenker, Pauline Reid, Anna L. Khattak, Muhammad A. Frank, Markus H. Millward, Michael Ziman, Mel Cancers (Basel) Article Cutaneous melanoma circulating tumour cells (CTCs) are phenotypically and molecularly heterogeneous. We profiled the gene expression of CTC subpopulations immunomagnetic-captured by targeting either the melanoma-associated marker, MCSP, or the melanoma-initiating marker, ABCB5. Firstly, the expression of a subset of melanoma genes was investigated by RT-PCR in MCSP-enriched and ABCB5-enriched CTCs isolated from a total of 59 blood draws from 39 melanoma cases. Of these, 6 MCSP- and 6 ABCB5-enriched CTC fractions were further analysed using a genome-wide gene expression microarray. The transcriptional programs of both CTC subtypes included cell survival maintenance, cell proliferation, and migration pathways. ABCB5-enriched CTCs were specifically characterised by up-regulation of genes involved in epithelial to mesenchymal transition (EMT), suggesting an invasive phenotype. These findings underscore the presence of at least two distinct melanoma CTC subpopulations with distinct transcriptional programs, which may have distinct roles in disease progression and response to therapy. MDPI 2019-01-30 /pmc/articles/PMC6406574/ /pubmed/30769764 http://dx.doi.org/10.3390/cancers11020157 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aya-Bonilla, Carlos
Gray, Elin S.
Manikandan, Jayapal
Freeman, James B.
Zaenker, Pauline
Reid, Anna L.
Khattak, Muhammad A.
Frank, Markus H.
Millward, Michael
Ziman, Mel
Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title_full Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title_fullStr Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title_full_unstemmed Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title_short Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles
title_sort immunomagnetic-enriched subpopulations of melanoma circulating tumour cells (ctcs) exhibit distinct transcriptome profiles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406574/
https://www.ncbi.nlm.nih.gov/pubmed/30769764
http://dx.doi.org/10.3390/cancers11020157
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