Protein Typing of Circulating Microvesicles Allows Real-Time Monitoring of Glioblastoma Therapy

Nat Med. 2012 Dec;18(12):1835-40. doi: 10.1038/nm.2994. Epub 2012 Nov 11.

Abstract

Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / chemistry*
  • Cell Line, Tumor
  • Glioblastoma / blood
  • Glioblastoma / drug therapy*
  • Glioblastoma / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles
  • Microfluidic Analytical Techniques
  • Transport Vesicles / chemistry*

Substances

  • Biomarkers, Tumor
  • Magnetite Nanoparticles