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

被引：14

作者：

Aya-Bonilla, Carlos ^{[1
]}

Gray, Elin S. ^{[1
]}

Manikandan, Jayapal ^{[2
]}

Freeman, James B. ^{[1
]}

Zaenker, Pauline ^{[1
]}

Reid, Anna L. ^{[1
]}

Khattak, Muhammad A. ^{[3
,4
]}

Frank, Markus H. ^{[1
,5
,6
,7
]}

Millward, Michael ^{[3
,4
]}

Ziman, Mel ^{[1
,8
]}

机构：

[1] Edith Cowan Univ, Sch Med & Hlth Sci, Perth, WA 6027, Australia

[2] NanoString Inc, Seattle, WA 98109 USA

[3] Univ Western Australia, Sch Med, Crawley, WA 6009, Australia

[4] Sir Charles Gairdner Hosp, Dept Med Oncol, Nedlands, WA 6009, Australia

[5] Harvard Med Sch, Boston Childrens Hosp, Transplantat Res Program, Boston, MA 02115 USA

[6] Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[7] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[8] Univ Western Australia, Sch Biomed Sci, Crawley, WA 6009, Australia

来源：

CANCERS | 2019年 / 11卷 / 02期

基金：

英国医学研究理事会;

关键词：

circulating tumour cells; melanoma; ABCB5; MCSP; gene expression; METASTATIC MELANOMA; EXPRESSION; IDENTIFICATION; HETEROGENEITY; ACTIVATION; RESISTANCE; PROTEINS; TARGETS; RNA;

D O I：

10.3390/cancers11020157

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：15

共 62 条

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