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Cell Rep. 2014 May 8;7(3):645-53. doi: 10.1016/j.celrep.2014.03.039. Epub 2014 Apr 18.

Isolation and molecular characterization of circulating melanoma cells.

Author information

1
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Bethesda, MD 20815, USA.
2
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
3
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
4
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
5
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
6
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
7
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA.
8
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Engineering in Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA.
9
Center for Engineering in Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
10
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
11
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: maheswaran@helix.mgh.harvard.edu.
12
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Howard Hughes Medical Institute, Bethesda, MD 20815, USA. Electronic address: haber@helix.mgh.harvard.edu.

Abstract

Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

PMID:
24746818
PMCID:
PMC4079008
DOI:
10.1016/j.celrep.2014.03.039
[Indexed for MEDLINE]
Free PMC Article

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