TY - JOUR
T1 - Immunomagnetic-enriched subpopulations of melanoma circulating tumour cells (CTCs) exhibit distinct transcriptome profiles
AU - Aya-Bonilla, Carlos
AU - Gray, Elin S.
AU - Manikandan, Jayapal
AU - Freeman, James B.
AU - Zaenker, Pauline
AU - Reid, Anna L.
AU - Khattak, Muhammad A.
AU - Frank, Markus H.
AU - Millward, Michael
AU - Ziman, Mel
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - ABCB5
KW - Circulating tumour cells
KW - Gene expression
KW - MCSP
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=85062386558&partnerID=8YFLogxK
U2 - 10.3390/cancers11020157
DO - 10.3390/cancers11020157
M3 - Article
AN - SCOPUS:85062386558
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 2
M1 - 157
ER -