Brain tumor cell invasion, anatomical and biological considerations

Gliomas exhibit diffuse infiltration into the normal brain parenchyma, and the tumor cells often show morphological features similar to reactive glia cells, making it difficult to discriminate tumor cells from other neural cell populations both in vitro and in vivo. Several methods have therefore been developed in order to observe migrating tumor cells in experimental tumor models. These include labeling of tumor cells with vital dyes as well as by using genetic markers. Despite the fact that these malignancies are highly invasive in the brain, they rarely metastazise out of the central nervous system (CNS). The dissemination of tumor cells is probably mediated both by passive cell displacement and by active cell migration. Tumor cells may be displaced within the brain by the passive flow of cerebrospinal fluid (CSF) within the perivascular space and along ventricular linings. Tumor growth and invasion occur in a micromillieu that is regulated both by cancer cells and normal cells. The biological attributes of invasion and cell migration include cell adhesion to extracellular matrix components, cell locomotion, and the ability to create space into which to move. This process is characterized by the degradation and turnover of ECM components, which implies the production of specific proteases and inhibitors. Tumor progression is also influenced by numerous growth factors which may stimulate the malignant cells both by paracrine and autocrine mechanisms. Tumor growth requires the persistent formation of new blood vessels and the induction of angiogenesis is most likely occurring during early stages of tumor development. This process is regulated both by several inducers and inhibitors of endothelial cell proliferation and migration.