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The Molecular Biology of Brain Metastasis

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Central Nervous System Metastasis, the Biological Basis and Clinical Considerations

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 18))

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Abstract

An understanding of the molecular biology of brain metastasis development is critical to the development of new preventatives and therapeutics. Our current understanding is largely based on functional validation studies of candidate genes in animal models. These candidates were either identified by genomic profiling of clinical specimens or brain-tropic cell lines, or were suspected factors in key steps of the brain metastatic process. This chapter provides a summary of current in vivo brain metastasis models, explores the key steps of brain metastasis development and discusses the experimental evidence that links various genes functionally to brain metastatic progression. Animal models have been developed for lung and breast carcinoma, and melanoma metastasis to the brain. Most commonly these models involve hematogenous metastasis from carotid artery or left cardiac ventricle injection, but implantation and spontaneous animal models have also been reported. The steps involved in brain metastatic spread include extravasation from the brain vasculature, tumor cell dormancy, and outgrowth in the brain microenvironment. The brain parenchyma is altered by a potent neuroinflammatory response, involving activated microglia and astrocytes that accompanies brain metastasis development both clinically and in animal models. Alterations in the expression levels of individual genes have demonstrated functional roles in brain metastasis development in animal models. This includes genes driving metastatic spread in general, for which functions in brain metastatic spread have been demonstrated, as well as those who appear to have brain metastasis specific roles. Genes involved in cell signaling, angiogenesis, microenvironment modulation, cell adhesion and invasion as well as multiple transcription factors are discussed.

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  1. Women’s Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, 37 Convent Drive, Bethesda, MD, 20892, USA

    Stephan Woditschka Ph.D., M.Sc., Brunilde Gril Ph.D., Lynda M. Evans Ph.D., L. Tiffany Reed DVM, DACVP & Patricia S. Steeg Ph.D.

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  1. Stephan Woditschka Ph.D., M.Sc.
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  2. Brunilde Gril Ph.D.
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  3. Lynda M. Evans Ph.D.
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  4. L. Tiffany Reed DVM, DACVP
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  5. Patricia S. Steeg Ph.D.
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Correspondence to Patricia S. Steeg Ph.D. .

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  1. , Laboratory of Molecular Pharmacology, National Cancer Institute, Convent Drive Building 3, Bethesda, 20892, Maryland, USA

    Diane Palmieri

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Woditschka, S., Gril, B., Evans, L.M., Reed, L.T., Steeg, P.S. (2012). The Molecular Biology of Brain Metastasis. In: Palmieri, D. (eds) Central Nervous System Metastasis, the Biological Basis and Clinical Considerations. Cancer Metastasis - Biology and Treatment, vol 18. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5291-7_2

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