The role of astrocytes in the progression of brain cancer: complicating the picture of the tumor microenvironment.
Gliomas and brain-metastatic tumors contribute to hundreds of thousands of deaths every year. Typical survival times for brain cancer patients, even with surgical, chemotherapy, and radiation treatment, remain very low despite advances in treatment. In brain cancers, astrocytes, which comprise approximately 50 % of the cells in the brain, become activated, resulting in a layer of reactive astrocytes surrounding the tumor. This process of reactive gliosis, which involves the secretion of growth factors and cytokines, helps repair injury in the brain, but also plays a role in disease progression. In this review, we survey the mechanisms by which astrocytes modulate the local tumor microenvironment, enhancing proliferation, invasion, chemoprotection, and immunoprotection of tumor cells. Consideration of the effect of astrocytes and reactive gliosis in in vitro and in vivo assays may allow us to obtain a more complete picture of the interactions occurring at the tumor microenvironment, which will provide additional insight into potential pathways that can be targeted by brain cancer therapeutics.
Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.|Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Amanda L
AL
Placone
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Alfredo
A
Quiñones-Hinojosa
Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA. searson@jhu.edu.|Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA. searson@jhu.edu.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA. searson@jhu.edu.
Peter C
PC
Searson
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
D005904:Glial Fibrillary Acidic Protein
Astrocytes; Glioma; Invasion; Proliferation; Reactive gliosis