Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes.
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.
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.
Chris L
CL
Smith
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Onur
O
Kilic
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Paula
P
Schiapparelli
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Hugo
H
Guerrero-Cazares
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Deok-Ho
DH
Kim
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Neda I
NI
Sedora-Roman
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.
Saksham
S
Gupta
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.
Thomas
T
O'Donnell
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Kaisorn L
KL
Chaichana
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Fausto J
FJ
Rodriguez
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sara
S
Abbadi
Department of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT 06516, USA.
JinSeok
J
Park
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: aquinon2@jhmi.edu.
Alfredo
A
Quiñones-Hinojosa
Department of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT 06516, USA. Electronic address: andre.levchenko@yale.edu.
Andre
A
Levchenko
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002465:Cell Movement; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016896:Treatment Outcome; D059016:Tumor Microenvironment
D010982:Platelet-Derived Growth Factor