Glioma invasion--pattern of dissemination by mechanisms of invasion and surgical intervention, pattern of gene expression and its regulatory control by tumorsuppressor p53 and proto-oncogene ETS-1.
The capacity of glioma cells to invade normal brain leads to far reaching dissemination of these tumors limiting surgical resection and the prospect of local treatment strategies. The analysis of the dissemination pattern, the molecular substrates and mechanisms involved suggest that glioma invasion most likely represents independent cellular behaviors leading to distinct pattern of spread. The search for common denominators of the invasive phenotype has demonstrated that invasive cells show gene expression profiles indicating elevated expression of motility associated genes and genes involved in resistance to apoptosis whereas proliferation and apoptosis related gene expression is repressed. Confirming these findings, invasive cells in vitro show elevated motility and resistance to drug induced apoptosis. Obviously invasiveness is an early event in the progression of glial tumors. Therefore, the loss of control over invasion genes must involve key elements of molecular tumor progression. We have recently demonstrated that deregulation of invasion gene expression occurs as a consequence of functional impairment of tumor suppressor p53 leading to unrestrained activation of proto-oncogene Ets-1 dependent invasion-associated genes. In this article the prospect of limiting the dissemination of glial tumors by anti-invasive strategies and targets for modulation of the invasive phenotype to reconstitute chemo- and radiation sensitivity are discussed.
Giese
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Department of Neurosurgery, University Hospital Luebeck, Germany. alf.giese@neurochirurgie.mu-luebeck.de
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C494041:ETS1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53