Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment

E.S. Gray, A.L. Reid, S. Bowyer, L. Calapre, K. Siew, R. Pearce, L. Cowell, M.H. Frank, Michael Millward, Melanie Ziman

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    66 Citations (Scopus)


    © 2015 The Society for Investigative Dermatology. Metastatic melanoma is a highly heterogeneous tumor; thus, methods to analyze tumor-derived cells circulating in blood should address this diversity. Taking this into account, we analyzed, using multiparametric flow cytometry, the co-expression of the melanoma markers melanoma cell adhesion molecule and melanoma-associated chondroitin sulphate proteoglycan and the tumor-initiating markers ATP-binding cassette sub-family B member 5 (ABCB5), CD271, and receptor activator of NF-κβ (RANK) in individual circulating tumor cells (CTCs) from 40 late-stage (III-IV) and 16 early-stage (I-II) melanoma patients. CTCs were heterogeneous within and between patients, with limited co-expression between the five markers analyzed. Analysis of patient matched blood and metastatic tumors revealed that ABCB5 and RANK subpopulations are more common among CTCs than in the solid tumors, suggesting a preferential selection for these cells in circulation. Pairwise comparison of CTC subpopulations longitudinally before and 6-13 weeks after treatment initiation showed that the percentage of RANK + CTCs significantly increased in the patients undergoing targeted therapy (N=16, P
    Original languageEnglish
    Pages (from-to)2040-2048
    JournalJournal of Investigative Dermatology
    Issue number8
    Early online date7 May 2015
    Publication statusPublished - Aug 2015


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