TY - JOUR
T1 - Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes
AU - Smith, Chris L.
AU - Kilic, Onur
AU - Schiapparelli, Paula
AU - Guerrero-Cazares, Hugo
AU - Kim, Deok Ho
AU - Sedora-Roman, Neda I.
AU - Gupta, Saksham
AU - O'Donnell, Thomas
AU - Chaichana, Kaisorn L.
AU - Rodriguez, Fausto J.
AU - Abbadi, Sara
AU - Park, Jin Seok
AU - Quiñones-Hinojosa, Alfredo
AU - Levchenko, Andre
N1 - Funding Information:
We thank H. Basdag, L. Johnson, and L. Noiman for establishing cell cultures; H. Nam Kim and K.Y. Suh for help in building nanopatterned surfaces; and M. Delannoy for assistance with SEM. This work was funded by NIH RO1 NS070024 (to A.Q.-H.), a Ford Foundation fellowship (to C.L.S.), AHA fellowship 13POST17140090 (to O.K.), and NIH grants U01CA15578 and CA16359 (Yale Cancer Center) (to A.L.).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2016.05.042
DO - 10.1016/j.celrep.2016.05.042
M3 - Article
C2 - 27292647
AN - SCOPUS:84975109838
SN - 2211-1247
VL - 15
SP - 2616
EP - 2624
JO - Cell Reports
JF - Cell Reports
IS - 12
ER -