Migration of human malignant astrocytoma cells in the mammalian brain: Scherer revisited

Abstract

Fresh suspensions of human glioblastoma multiforme were preincubated in the plant lectin Phaseolus vulgaris leucoagglutinin (PHAL) and implanted into cortical pockets in adult rat brain. Brains were investigated periodically over 30 postoperative days and the migration of the human glioblastoma cells was traced with anti-PHAL immunofluorescence or the overexpression of human specific p185c-neu a specific marker of a class of human malignant astrocytoma cells. The principal pathway of migration of the implanted human cells in the rat brain was ventrally through cortical gray matter and into the corpus callosum, with rapid lateral distribution in this and other parallel and intersecting white matter fascicles. Human glioblastoma cells also migrated on basement membrane lined blood vessels, pia-glia membrane and spaces of Virchow-Robin, as well as the subependymal space of the ventricles. These paths of migration of human glioblastoma cells in the rat brain are consistent with the pathways of spread of glioblastoma in the human brain as described by Scherer over 50 years ago, indicating that multifocal malignant astrocytomas have common migratory pathways in mature mammalian brain.

The Histopathological Spectrum of Primary Human Glioblastomas with Relations to Tumour Biology

“…The high frequency of secondary structures of Scherer [14] (73/152, 48%) clearly demonstrates the infiltrative nature of diffuse astrocytomas and represents the main cause for non-radical tumour resection and the high recurrence rate [13,26]. In agreement with Scherer [14] these features commonly occurred in combination with a strong correlation between perineural and perivascular growth (p < 0.001).…”

“…For instance, hypoxic pseudopalisading cells can induce glioma angiogenesis and serve as a link between necrosis and microvascular proliferation [10][11][12]. Further, the secondary features of Scherer have been related to the infiltrative properties of neoplastic astrocytes [13,14].…”

Tenascin-C Stimulates Glioma Cell Invasion through Matrix Metalloproteinase-12

“…These ECM molecules include vitronectin, collagen I, collagen IV, osteopontin, tenascin-C, secreted protein acidic and rich in cysteine, and brain enriched hyaluronan binding (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Glioma invasion is thought to occur along ECM protein-containing structures, such as along tracts of myelinated fibers (22)(23)(24). Besides creating a more permissive substrate for invasiveness, ECM proteins can also affect other tumorigenic properties, such as survival, cell cycle progression, and angiogenesis.…”

Analysis of Tissue Chimerism in Nude Mouse Brain and Abdominal Xenograft Models of Human Glioblastoma Multiforme: What Does It Tell Us About the Models and About Glioblastoma Biology and Therapy?

“…Similar results should be achieved with pools of terminally labeled oligonucleotides whose sequences are complementary with Alu sequences or with probes generated by the polymerase chain reaction, using mouse or human DNA as a template and oligonucleotides, the sequences of which are complementary to the Alu sequence, as primers. For cell migration studies in transplantation chimeras, these ISH methods should take the place of other marker systems, such as (a) the prelabeling of cells with fluorescent vital dyes or lectins, because such tracers are necessarily progressively washed out due to halving of their amount on each cell division, allowing tumor cell migration studies for only 3-4 weeks (Bernstein et al 1989;Laws et al 1993), and (b) the transfer of non-human genetic material into the GBM cells, such as the lacZ gene that codes for a bacterial ␤ -galactosidase for which the enzyme activity can be detected in histological sections (Lampson et al 1993;Pedersen et al 1995). Indeed, transfection might select subsets of human brain tumor cells or alter their invasiveness.…”