Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2017 Feb 20;36(26):3749–3759. doi: 10.1038/onc.2017.1

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Copyright © 2017 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

PMC Copyright notice

Increased M2 macrophages at the tumor edge associated with bevacizumab-resistant glioblastoma. (a) Human glioblastomas (n=8/group) exhibited increased IBA1⁺ macrophages upon becoming bevacizumab-resistant compared to paired pre-treatment bevacizumab-naive specimens (P=0.02), while no such increase occurred in bevacizumab-naive glioblastomas after recurrence compared with before (P=0.8) Y-axis represents percent of the high-powered field that was immunopositive as derived by ImageJ software. (b) Absolute qPCR for microglia marker CX3CR1 and myeloid macrophage marker CCR2 on CD11b⁺ cells isolated from site-directed biopsies of the central core, enhancing edge, and infiltrated white matter of patient glioblastomas revealed that the ratio of CCR2:CX3CR1 expression increased robustly in all sites of bevacizumab-resistant (n=3) versus bevacizumab-naive (n=5) glioblastomas (P=0.006 central core; P=0.01 enhancing edge; P=0.02 infiltrated white matter) (c) U87-Bev^S and U87-Bev^R intracranial xenografts exhibited increased CD11b⁺ macrophages (red) upon treatment with bevacizumab compared with treatment with IgG (P=0.01). These macrophages were recruited to the tumor (green) edge (n=5/group). (d) THP-1 human monocytes exhibited decreased chemotaxis in response to U87-Bev^R conditioned media (CM) compared with U87-Bev^S CM (P<0.0001) (n=4/group), whereas (e) murine bone marrow derived macrophages had greater cell numbers when cultured in U87-Bev^R conditioned media for 48 h compared with U87-Bev^S conditioned media (P=0.04), with both U87-Bev^R (P<0.001) and U87-Bev^S (P=0.04) conditioned media increasing macrophage numbers (n=8/group). (f) qPCR of FACS-sorted CD11b⁺ TAMs isolated from intracranial U87-Bev^R and U87-Bev^S xenograft (n=5/group) revealed increased M2 macrophages in U87-Bev^R intracranial xenografts relative to U87-Bev^S intracranial xenografts, independent of treatment (P<0.0001), as revealed by M2/M1 polarization ratios determined by multiplying the qPCR fold increases in three different M2 primers divided by the qPCR fold increases in three different M1 primers normalized to results for U87-Bev^S xenografts treated with IgG.