TY - JOUR
T1 - Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment
AU - Gray, E.S.
AU - Reid, A.L.
AU - Bowyer, S.
AU - Calapre, L.
AU - Siew, K.
AU - Pearce, R.
AU - Cowell, L.
AU - Frank, M.H.
AU - Millward, Michael
AU - Ziman, Melanie
PY - 2015/8
Y1 - 2015/8
N2 - © 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
AB - © 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
U2 - 10.1038/jid.2015.127
DO - 10.1038/jid.2015.127
M3 - Article
C2 - 25830652
SN - 0022-202X
VL - 135
SP - 2040
EP - 2048
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 8
ER -