Abstract
In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.
Highlights
Central nervous system (CNS) malignancies include primary brain tumors that originate within the brain, and brain metastases which are initiated upon the dissemination of cancer cells from the primary
These include growth of cancer cells around the pre-existing blood vessels, sprouting of vessels, and vasculogenesis which is a recruitment of endothelial progenitor cells (EPCs) that have been proposed to originate from different sources, including the bone marrow, the existing vasculature, or adipose tissue; reviewed in [30,31]
The complex role of the tumor microenvironment in the progression of brain tumors is still poorly understood and we are just starting to understand the interactions between cancer cells and stromal cells in the brain
Summary
Central nervous system (CNS) malignancies include primary brain tumors that originate within the brain, and brain metastases which are initiated upon the dissemination of cancer cells from the primary. Brain metastases develop in 10–25% of cancer patients with extracranial malignancies and account for more than half of all brain tumors in adults. Despite recent improvements in the treatment of brain metastases, the median survival time of patients with metastatic brain lesions is only 7–16 months [1,2,3,4]. Gliomas are the most common primary brain tumors and include a variety of histologic and molecular types. In addition to cancer cells, tumor lesions contain a mixture of different stromal cells This for example includes endothelial cells (EC) that constitute blood vessels, as well as inflammatory cells that infiltrate tumors from the blood stream. This review seeks to summarize our current understanding of interactions between tumor cells and the three cell types in the brain tumor microenvironment that have been so far most extensively studied, namely brain endothelial cells, cells of myeloid origin (e.g., microglia/macrophages), and astrocytes (Figure 1)
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