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Cell Rep. 2016 Jun 21;15(12):2616-24. doi: 10.1016/j.celrep.2016.05.042. Epub 2016 Jun 9.

Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes.

Author information

1
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
2
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
3
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
4
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
5
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
6
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
7
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
8
Department of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT 06516, USA.
9
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: aquinon2@jhmi.edu.
10
Department of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT 06516, USA. Electronic address: andre.levchenko@yale.edu.

Abstract

Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative, but it places a high premium on the precision of in vitro methods and the relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here, we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

PMID:
27292647
PMCID:
PMC5517094
DOI:
10.1016/j.celrep.2016.05.042
[Indexed for MEDLINE]
Free PMC Article
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