Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment
Elin S. Gray, Edith Cowan UniversityFollow
Anna L. ReidFollow
Leslie Calapre, Edith Cowan UniversityFollow
Robert Pearce, Edith Cowan University
Markus H. Frank
Mel R. Ziman Dr, Edith Cowan UniversityFollow
Nature Publishing Group
Faculty of Health, Engineering and Science
School of Medical Sciences
National Health and Medical Research Council
NHMRC Number : 1013349
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
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.
Gray, E. S., Reid, A. L., Bowyer, S., Calapre, L., Siew, K., Pearce, R., ... & Ziman, M. (2015). Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment. Journal of Investigative Dermatology. vol. 135,(8), pp. 2040-2048. Available here.