Brain Tumor Cells in Circulation Are Enriched for Mesenchymal Gene Expression

作者：Sullivan James P; Nahed Brian V; Madden Marissa W; Oliveira Samantha M; Springer Simeon; Bhere Deepak; Chi Andrew S; Wakimoto Hiroaki; Rothenberg S Michael; Sequist Lecia V; Kapur Ravi; Shah Khalid; Iafrate A John; Curry William T; Loeffler Jay S; Batchelor Tracy T; Louis David N; Toner Mehmet; Maheswaran Shyamala^*; Haber Daniel A

来源：Cancer Discovery, 2014, 4(11): 1299-1309.

DOI：10.1158/2159-8290.CD-14-0471

Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination is extremely rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTC). Staining and scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), and then applied clinically: CTCs were identified in at least one blood specimen from 13 of 33 patients (39%; 26 of 87 samples). Single GBM CTCs isolated from both patients and mouse PDX models demonstrated enrichment for mesenchymal over neural differentiation markers compared with primary GBMs. Within primary GBMs, RNA in situ hybridization identified a subpopulation of highly migratory mesenchymal tumor cells, and in a rare patient with disseminated GBM, systemic lesions were exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades the vasculature and may proliferate outside the brain.

• 出版日期2014-11