Isolation and molecular characterization of circulating melanoma cells

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Cell Line, Tumor
  • Cell Separation
  • Humans
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microfluidic Analytical Techniques
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / metabolism*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / metabolism
  • Sequence Analysis, RNA
  • Tamoxifen / pharmacology
  • Transcriptome / drug effects

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf
  • PTEN Phosphohydrolase