Isolation and Molecular Characterization of Circulating Melanoma Cells

Xi Luo; Devarati Mitra; Ryan J. Sullivan; Ben S. Wittner; Anya M. Kimura; Shiwei Pan; Mai P. Hoang; Brian W. Brannigan; Donald P. Lawrence; Keith T. Flaherty; Lecia V. Sequist; Martin McMahon; Marcus W. Bosenberg; Shannon L. Stott; David T. Ting; Sridhar Ramaswamy; Mehmet Toner; David E. Fisher; Shyamala Maheswaran; Daniel A. Haber

doi:10.1016/j.celrep.2014.03.039

Cell Reports (May 2014)

Isolation and Molecular Characterization of Circulating Melanoma Cells

Xi Luo,
Devarati Mitra,
Ryan J. Sullivan,
Ben S. Wittner,
Anya M. Kimura,
Shiwei Pan,
Mai P. Hoang,
Brian W. Brannigan,
Donald P. Lawrence,
Keith T. Flaherty,
Lecia V. Sequist,
Martin McMahon,
Marcus W. Bosenberg,
Shannon L. Stott,
David T. Ting,
Sridhar Ramaswamy,
Mehmet Toner,
David E. Fisher,
Shyamala Maheswaran,
Daniel A. Haber

Affiliations

Xi Luo: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Devarati Mitra: Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
Ryan J. Sullivan: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Ben S. Wittner: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Anya M. Kimura: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Shiwei Pan: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Mai P. Hoang: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Brian W. Brannigan: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Donald P. Lawrence: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Keith T. Flaherty: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Lecia V. Sequist: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Martin McMahon: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA
Marcus W. Bosenberg: Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA
Shannon L. Stott: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
David T. Ting: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Sridhar Ramaswamy: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Mehmet Toner: Center for Engineering in Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA
David E. Fisher: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Shyamala Maheswaran: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Daniel A. Haber: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA

DOI: https://doi.org/10.1016/j.celrep.2014.03.039
Journal volume & issue: Vol. 7, no. 3
pp. 645 – 653

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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