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

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.

[1]  E R Laws,et al.  Human malignant astrocytoma xenografts migrate in rat brain: A model for central nervous system cancer research , 1989, Journal of neuroscience research.

[2]  R. Bjerkvig,et al.  Multicellular tumor spheroids from human gliomas maintained in organ culture. , 1990, Journal of Neurosurgery.

[3]  E. Laws,et al.  Chemotherapeutic trials on human malignant astrocytomas in organ culture. , 1977, Journal of neurosurgery.

[4]  A. Kaye,et al.  Development of a xenograft glioma model in mouse brain. , 1986, Cancer research.

[5]  S. Vandenberg Current Diagnostic Concepts of Astrocytic Tumors , 1992, Journal of neuropathology and experimental neurology.

[6]  E R Laws,et al.  Immunohistochemistry of human malignant astrocytoma cells xenografted to rat brain: apolipoprotein E. , 1989, Neurosurgery.

[7]  R. Coleman,et al.  In vivo imaging of intracranial human glioma xenografts comparing specific with nonspecific radiolabeled monoclonal antibodies. , 1986, Journal of neurosurgery.

[8]  Lawrence R. Wood,et al.  C6 glioma cell invasion and migration of rat brain after neural homografting: ultrastructure. , 1990 .

[9]  H. Scherer Structural Development in Gliomas , 1938 .

[10]  K. Petruk,et al.  Development of a large-animal human brain tumor xenograft model in immunosuppressed cats. , 1991, Cancer research.

[11]  P. Burger,et al.  The morphologic effects of radiation administered therapeutically for intracranial gliomas.A Postmortem study of 25 cases , 1979, Cancer.

[12]  J. J. Bernstein,et al.  Fetal cortical astrocytes migrate from cortical homografts throughout the host brain and over the glia limitans , 1988, Journal of neuroscience research.

[13]  J. Rutka Effects of Extracellular Matrix Proteins on the Growth and Differentiation of an Anaplastic Glioma Cell Line , 1986, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[14]  L D Lunsford,et al.  Radiobiology of radiosurgery: Part II. The rat C6 glioma model. , 1992 .

[15]  R. Lund,et al.  Migration of astrocytes transplanted to the midbrain of neonatal rats , 1992, The Journal of comparative neurology.

[16]  V. P. Collins,et al.  Interspecies identification of astrocytes after intracerebral transplantation. , 1986, Developmental Neuroscience.

[17]  J. Kepes Astrocytomas: Old and Newly Recognized Variants, Their Spectrum of Morphology and Antigen Expression , 1987, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[18]  N. Baumann,et al.  Migration patterns of donor astrocytes after reciprocal striatum–cerebellum transplantation into newborn hosts , 1991, Journal of neuroscience research.

[19]  E. Laws,et al.  Individual C6 glioma cells migrate in adult rat brain after neural homografting , 1991, International Journal of Developmental Neuroscience.

[20]  Richard B. Richter,et al.  Pathology of Tumors of the Nervous System. , 1964 .

[21]  D. Bigner,et al.  Growth and Chemotherapeutic Response in Athymic Mice of Tumors Arising from Human Glioma‐derived Cell Lines , 1981, Journal of neuropathology and experimental neurology.

[22]  I. Suard,et al.  Survival of astroglial cell lineage from adult brain transplant. , 1989, Developmental Neuroscience.

[23]  H. Scherer,et al.  THE FORMS OF GROWTH IN GLIOMAS AND THEIR PRACTICAL SIGNIFICANCE , 1940 .

[24]  L. de Ridder,et al.  Invasion of human brain tumors in vitro: relationship to clinical evolution. , 1990, Journal of neurosurgery.

[25]  E. Laws,et al.  Human-specific c-neu proto-oncogene protein overexpression in human malignant astrocytomas before and after xenografting. , 1993, Journal of neurosurgery.

[26]  N. Malamud,et al.  THE PROBLEM OF MULTICENTRIC GLIOMAS. , 1963, Journal of neurosurgery.

[27]  E. B. Jackson,et al.  Effects of Colchicine and Radiation on Growth of Normal Tissues and Tumors , 1940 .