Mechanisms of tumor cell invasion and angiogenesis in the central nervous system

Abstract

Despite extensive progress in characterizing the genetic events involved in the development of gliomas, the cellular origin and the defined molecular mechanisms that lead to their occurrence are still unclear. It is known that tumours are of monoclonal origin. This is contrasted by the fact that gliomas frequently express features of different glial cell lineages. With the identification of pluripotent neural stem cells and the growth factors that control neural cell development, we are now making early inroads towards understanding glial cell migration as well as the neural cell plasticity within the adult central nervous system (CNS). Gliomas share several fetal antigens with immature brain cells. It is therefore tempting to speculate that the migration of neural precursor cells actually represents the normal counterpart of glioma cell migration. The migratory behavior of gliomas may be due to a predetermined interplay between normal brain tissue and the migrating cells, where the brain represents a permissive tissue for guiding cells with certain phenotypic traits to migrate along specific anatomical structures. Malignant progression is also accompanied by extensive angiogenesis which is especially prominent in glioblastoma multiforme (GBM). For cell proliferation to take place, several cell signaling cues mediated by specific growth factors are shared between the glioma cells and the endothelial cells while others are unique for endothelial cells. Therefore the endothelial cell compartment represents a promising target for novel therapeutic strategies including gene therapy and cell-based therapies.

A Synthetic dl-Nordihydroguaiaretic acid (Nordy), Inhibits Angiogenesis, Invasion and Proliferation of Glioma Stem Cells within a Zebrafish Xenotransplantation Model

“…In addition, the positive correlation between angiogenesis and invasion induced by GSCs within zebrafish embryos suggested that more newly formed vessels may offer a convenient route for GSCs invasion in vivo . This is similar to the phenotypes seen in our previously described work [34]. Furthermore, suppression of angiogenesis by Nordy might in turn inhibit GSC invasion.…”

In vivo distribution of U87MG cells injected into the lateral ventricle of rats with spinal cord injury

“…CSF is watery fluid that is continuously produced in choroid plexuses of ventricles in the brain and absorbed into the venous system around the surface of the brain [ 29 ]. The mean CSF volume is 150 ml in human, including 25 ml in ventricles and 125 ml in the subarachnoid space [ 30 ]. CSF circulation from sites of production to sites of absorption largely depends on arterial pulse wave.…”

A tumor-macrophage interaction model with fuzzy initial values

“…Genetic alterations that lead to malignant phenotypes have been identified [1,2], and mechanisms necessary to sustain a solid tumor [3] and that contribute to tumor-cell invasion [4,5]. Mathematical modeling of both tumor growth and angiogenesis have been active areas of research.…”