Migration of fresh human malignant astrocytoma cells into hydrated gel wafers in vitro.

Individual astrocytoma cells expressing a cytoplasmic form of pl85 c-neu migrated along basement membrane lined surfaces after xenografing fresh low or high grade human malignant astrocytomas into host rat brain. We now study the migratory capacity of fresh human malignant astrocytoma cells seeded on hydrated gel wafers composed of artificial basement membrane or collagen I, a normal and lesion-related CNS extracellular matrix component. Approximately 107 mechanically disrupted cells (with small clumps) of 3 fresh low grade and 6 fresh high grade astrocytomas were seeded on the surface of artificial basement membrane and collagen I wafers (11 × 16 mm). The wafers were then prepared for scanning electron microscopy and immunohistochemstry at 1, 3, 5, and 7 days after seeding. Regardless of tumor grade, a morphologically similar class of cells was observed to migrate through collagen I gels in 24 hours and 0.5–1.5 mm into artificial basement membrane gels in 7 days. Immunohistochemistry revealed that the migrated cells from low and high grade astrocytomas were positive for glial fibrillary acidic protein (GFAP)) and expressed cytoplasmic human-specific pl85 c-neu . These data indicate that fresh human malignant astrocytoma cells that contain GFAP and express cytoplasmic pl85 c-neu have a high degree of migratory capacity and could be the cell in the tumor involved in intraparenchymal metastasis and poor patient survival in high grade astrocytomas of the human brain.

[1]  J. Bacus,et al.  HER-2/neu oncogene expression and proliferation in breast cancers. , 1990, The American journal of pathology.

[2]  B. Scheithauer,et al.  AN ATLAS OF NEUROPATHOLOGY , 1949 .

[3]  W. J. Brammar,et al.  Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. , 1987, Oncogene.

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

[5]  D. Bigner Biology of gliomas: potential clinical implications of glioma cellular heterogeneity. , 1981, Neurosurgery.

[6]  H. Roels,et al.  The neu‐oncogene protein as a predictive factor for haematogenous metastases in breast cancer patients , 1990, International journal of cancer.

[7]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[8]  G. Clark,et al.  Amplification of c-erbB-2 and aggressive human breast tumors? , 1988, Science.

[9]  D. Slamon,et al.  HER-2/neu oncogene amplification and expression in breast and ovarian cancers. , 1990, Progress in clinical and biological research.

[10]  A. Komiyama,et al.  Expression of the neu oncogene under the transcriptional control of the myelin basic protein gene in transgenic mice: Generation of transformed glial cells , 1992, Journal of neuroscience research.

[11]  T. Nakamura,et al.  Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. , 1993, British Journal of Cancer.

[12]  A. Ullrich,et al.  Expression of the p185 encoded by her2 oncogene in normal and transformed human tissues , 1990, International journal of cancer.

[13]  C. Bucana,et al.  Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites. , 1989, Journal of the National Cancer Institute.

[14]  H. Scherer A CRITICAL REVIEW , 1940, Journal of neurology and psychiatry.

[15]  E. Laws,et al.  Mechanisms of C6 glioma cell and fetal astrocyte migration into hydrated collagen I gels , 1992, Brain Research.

[16]  Y. Yarden,et al.  Receptor tyrosine kinase expression in astrocytic lesions: similar features in gliosis and glioma. , 1993, Neurosurgery.

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

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

[19]  R F MABON,et al.  A simplified classification of the gliomas. , 1949, Proceedings of the staff meetings. Mayo Clinic.

[20]  N. Nomura,et al.  Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor , 1986, Nature.

[21]  J. Starkey,et al.  Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines. , 1989, Cancer research.

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

[23]  L. Reid,et al.  Clonal growth of tumors on tissue-specific biomatrices and correlation with organ site specificity of metastases. , 1989, Cancer research.

[24]  M. Yoshida,et al.  Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line , 1986, Molecular and cellular biology.

[25]  V. Arena,et al.  Survival of Patients with Well-Differentiated Astrocytomas Diagnosed in The Era of Computed Tomography , 1991 .

[26]  P J Kelly,et al.  Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. , 1993, Journal of neurosurgery.

[27]  R. Koski,et al.  Neu differentiation factor: A transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit , 1992, Cell.

[28]  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.

[29]  J. J. Bernstein,et al.  Sequestering of immunoglobulins by astrocytes after cortical lesion and homografting of fetal cortex , 1993, International Journal of Developmental Neuroscience.

[30]  A. Schor,et al.  The use of three‐dimensional collagen gels for the study of tumour cell invasion in vitro: Experimental parameters influencing cell migration into the gel matrix , 1982, International journal of cancer.

[31]  W F Taylor,et al.  Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres. , 1984, Journal of neurosurgery.

[32]  M. Watatani,et al.  Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Bast,et al.  Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. , 1991 .

[34]  M. Waterfield,et al.  Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system , 1993, Nature.

[35]  N. Lemoine,et al.  The c‐erbB‐2 proto‐oncogene in human pancreatic cancer , 1990, The Journal of pathology.

[36]  R. Martuza,et al.  Glial growth factor—like activity in Schwann cell tumors , 1986, Annals of neurology.

[37]  S. Green,et al.  Glioblastoma multiforme and anaplastic astrocytoma pathologic criteria and prognostic implications , 1985, Cancer.

[38]  I. Verma,et al.  Expression of cellular oncogenes in human malignancies. , 1984, Science.

[39]  B A Kall,et al.  Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. , 1987, Journal of neurosurgery.

[40]  A. Nikitin,et al.  Early mutation of the neu (erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[41]  B. Scheithauer,et al.  Surgical Pathology of the Nervous System and its Coverings , 1976 .

[42]  Edward R. Laws,et al.  Migration of human malignant astrocytoma cells in the mammalian brain: Scherer revisited , 1993, International Journal of Developmental Neuroscience.

[43]  K. West,et al.  c-erbB-2 oncogene product expression and prognosis in gastric carcinoma. , 1992, Journal of clinical pathology.

[44]  W. McGuire,et al.  HER-2/neu amplification predicts poor survival in node-positive breast cancer. , 1990, Cancer research.