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Abstract Details

AbstractDetails

Abstract Date: 5/2/2015

Author(s):
Brian Nahed, MD
James Sullivan, PhD
Marissa Madden, BS
Samantha Oliveira, BS
Simeon Springer, BS
Deepak Bhere, BS
Andrew Chi, MD, PhD
Hiroaki Wakimoto, MD
Tracy Batchelor, MD
David Louis, MD, PhD
Mehmet Toner, PhD
Shyamala Maheswaran, PhD
Daniel Haber, MD, PhD (Boston, MA)

Introduction

Glioblastoma has been characterized into four transcriptional subtypes: proneural, neural, classical and mesenchymal. Circulating tumor cells (CTC) have recently been identified in the patients with Glioblastoma (GBM).  Using a novel microfluidic capture device, the CTC iChip, we hypothesize that GBM CTC can be isolated and characterized according to these transcriptional subtypes.


Methods

Using the CTC-iChip, we captured CTCs from whole blood via immunomagnetic depletion of hematopoetic cells in both patient and mouse xenograft models.  CTCs were identified using a GBM-specific antibody cocktail, which has been previously validated. Quantitative RT-PCR was performed on CTCs identifying gene expression signatures corresponding to the four transcriptional subtypes of GBM.  The patient CTCs were compared with their matched primary tumor, and the xenograft CTCs were compared with single tumor cells from matched xenografts. 


Results

Single GBM CTCs (n=15) were isolated from the blood of patients (n = 7) and mouse xenografts. Patient-derived CTCs demonstrated mesenchymal transcripts and down regulation of neural and oligodendroglial lineage markers compared with matched primary tumor specimens. Similarly, CTC xenograft models also demonstrated similar mesenchymal differentiation. Using RNA in-situ hybridization, we identified mesenchymal subpopulations within primary tumor specimens which were predominantly found around areas of necrosis or vascular proliferation.


Conclusions

GBM CTCs in patients demonstrate mesenchymal differentiation. RNA in-situ hybridization identifies mesenchymal subpopulations in the primary tumor which may correspond to those CTCs identified in the blood of Glioblastoma patients. Further characterization is necessary to define the role of CTC in understanding and treating patients with Glioblastoma.

Keywords:

Article ID: AA-31545


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