Abstract
The initial event in the generation of all central nervous system (CNS) tumors is the transformation of a normal cell into a cancer cell. The biological processes associated with this development eventually lead to the survival of cancer cells and to the formation of a solid tumor. Steps involved in this tumorigenic process include the cell¡¯s escape from the immune system surveillance (i.e., antitumor response), aberrant proliferation and multiplication, tumor cell invasion, and angiogenesis. Over the past decade, much has been learned about the basic genetic events and the molecular biology underlying the development of CNS cancers.This review attempts to describe the molecular biology of CNS tumors, highlighting potential targets for therapeutic interventions.
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References
Agarwal M L, Agarwal A, Taylor W R and Stark G R (1995) p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci U S A 92: 8493¨C8497
Apodaca G, Rutka J T, Bouhana K, Berens M E, Giblin J R, Rosenblum M L, McKerrow J H and Banda M J (1990) Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res 50: 2322¨C2329
Aruffo A, Stamenkovic I, Melnick M, Underhill C B and Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61: 1303¨C1313
Ashkenazi A and Dixit V M (1998) Death receptors: signaling and modulation. Science 281: 1305¨C1308
Ashley D M, Faiola B, Nair S, Hale L P, Bigner D D and Gilboa E (1997) Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J Exp Med 186: 1177¨C1182
Barker F G, Chen P, Furman F, Aldape K D, Edwards M S and Israel M A (1997) P16 deletion and mutation analysis in human brain tumors. J Neurooncol 31: 17¨C23
Bertolotto A, Magrassi M L, Orsi L, Sitia C and Schiffer D (1986) Glycosaminoglycan changes in human gliomas. A biochemical study. J Neurooncol 4: 43¨C48
Beutler B and van Huffel C (1994) Unraveling function in the TNF ligand and receptor families [comment]. Science 264: 667¨C668
Bhondeley M K, Mehra R D, Mehra N K, Mohapatra A K, Tandon P N, Roy S and Bijlani V (1988) Imbalances in T cell subpopulations in human gliomas. J Neurosurg 68:589¨C593
Bourdon M A and Ruoslahti E (1989) Tenascin mediates cell attachment through an RGD-dependent receptor. J Cell Biol 108: 1149¨C1155
Cheng S Y, Huang H J, Nagane M, Ji X D, Wang D, Shih C C,Arap W, Huang C M and Cavenee W K (1996) Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci U S A 93: 8502¨C8507
Chicoine M R and Silbergeld D L (1995) Assessment of brain tumor cell motility in vivo and in vitro. J Neurosurg 82:615¨C622
Chinnaiyan A M, Tepper C G, Seldin M F, O¡¯Rourke K, Kischkel F C, Hellbardt S, Krammer P H, Peter M E and Dixit V M (1996) FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptorinduced apoptosis. J Biol Chem 271: 4961¨C4965
Cohen S, Ushiro H, Stoscheck C and Chinkers M (1982) A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J Biol Chem 257: 1523¨C1531
Costello J F, Berger M S, Huang H S and Cavenee W K (1996) Silencing of p16/CDKN2 expression in human gliomas by methylation and chromatin condensation. Cancer Res 56:2405¨C2410
Delpech B, Maingonnat C, Girard N, Chauzy C, Maunoury R, Olivier A, Tayot J and Creissard P (1993) Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma. Eur J Cancer 7: 1012¨C1017
Dirks P B, Hubbard S L, Murakami M and Rutka J T (1997) Cyclin and cyclin-dependent kinase expression in human astrocytoma cell lines. J Neuropathol Exp Neurol 56: 291¨C300
El-Deiry W S, Harper J W, O¡¯Connor P M, Velculescu V E, Canman C E, Jackman J, Pietenpol J A, Burrell M, Hill D E, Wang Y and et al. (1994) WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54: 1169¨C1174
Ennis B W and Matrisian L M (1994) Matrix degrading metalloproteinases. J Neurooncol 18: 105¨C109
Finkel E (1999) Does cancer therapy trigger cell suicide? [news]. Science 286: 2256¨C8
Fraser A, McCarthy N and Evan G I (1996) Biochemistry of cell death. Curr Opin Neurobiol 6: 71¨C80
Fueyo J, Gomez-Manzano C, Yung W K and Kyritsis A P (1998) The functional role of tumor suppressor genes in gliomas: clues for future therapeutic strategies. Neurology 51: 1250¨C1255
Fulci G and Van Meir E G (1999) p53 and the CNS: tumors and developmental abnormalities. Mol Neurobiol 19: 61¨C77
Giese A, Laube B, Zapf S, Mangold U and Westphal M (1998) Glioma cell adhesion and migration on human brain sections.Anticancer Res 18: 2435¨C2447
Giese A, Loo M A, Rief M D, Tran N and Berens M E (1995) Substrates for astrocytoma invasion. Neurosurgery 37:294¨C301; discussion 301¨C302
Giese A and Westphal M (1996) Glioma invasion in the central nervous system. Neurosurgery 39: 235¨C50; discussion 250¨C252
Gladson C L and Cheresh D A (1991) Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest 88: 1924¨C1932
Gomez-Manzano C, Fueyo J, Kyritsis A P, Steck P A, Roth J A, McDonnell T J, Steck K D, Levin V A and Yung W K (1996) Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56: 694¨C699
Gordon L B, Nolan S C, Cserr H F, Knopf P M and Harling- Berg C J (1997) Growth of P511 mastocytoma cells in BALB/c mouse brain elicits CTL response without tumor elimination: a new tumor model for regional central nervous system immunity. J Immunol 159: 2399¨C2408
Gross J L, Behrens D L, Mullins D E, Kornblith P L and Dexter D L (1988) Plasminogen activator and inhibitor activity in human glioma cells and modulation by sodium butyrate. Cancer Res 48: 291¨C296
Guan J L and Shalloway D (1992) Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 358: 690¨C692
Guerin C and Laterra J (1997) Regulation of angiogenesis in malignant gliomas. Exs 79: 47¨C64
Gutmann D H, Giordano M J, Fishback A S and Guha A (1997) Loss of merlin expression in sporadic meningiomas, ependymomas and schwannomas. Neurology 49: 267¨C270
Gutmann D H, Sherman L, Seftor L, Haipek C, Hoang Lu K and Hendrix M (1999) Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility,adhesionand spreading. Hum Mol Genet 8: 267¨C275
Halaka A N, Bunning R A, Bird C C, Gibson M and Reynolds J J (1983) Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro. J Neurosurg 59:461¨C466
Hanahan D and Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.Cell 86: 353¨C364
Haupt Y, Maya R, Kazaz A and Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296¨C299
He J, Olson J J and James C D (1995) Lack of p16INK4 or retinoblastoma protein (pRb), or amplification-associated overexpression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines. Cancer Res 55: 4833¨C4836
Hermanson M, Funa K, Koopmann J, Maintz D, Waha A, Westermark B, Heldin C H, Wiestler O D, Louis D N, von Deimling A and Nister M (1996) Association of loss of heterozygosity on chromosome 17p with high plateletderived growth factor alpha receptor expression in human malignant gliomas. Cancer Res 56: 164¨C171
Higuchi M, Ohnishi T, Arita N, Hiraga S and Hayakawa T (1993) Expression of tenascin in human gliomas: its relation to histological malignancy, tumor dedifferentiation and angiogenesis. Acta Neuropathol 85: 481¨C487
Hsu S C, Volpert O V, Steck P A, Mikkelsen T, Polverini P J, Rao S, Chou P and Bouck N P (1996) Inhibition of angiogenesis in human glioblastomas by chromosome 10 induction of thrombospondin-1. Cancer Res 56: 5684¨C5691
Hynes R O (1987) Integrins: a family of cell surface receptors. Cell 48: 549¨C554
Ichimura K, Schmidt E E, Goike H M and Collins V P (1996) Human glioblastomas with no alterations of the CDKN2 A (p16INK4 A, MTS1) and CDK4 genes have frequent mutations of the retinoblastoma gene. Oncogene 13: 1065¨C1072
Joki T, Kikuchi T, Akasaki Y, Saitoh S, Abe T and Ohno T (1999) Induction of effective antitumor immunity in a mouse brain tumor model using B7¨C1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12. Int J Cancer 82: 714¨C720
Kastan M B, Onyekwere O, Sidransky D, Vogelstein B and Craig R W (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304¨C6311
Ko L J and Prives C (1996) p53: puzzle and paradigm. Genes Dev 10: 1054¨C1072
Koff A, Ohtsuki M, Polyak K, Roberts J M and Massague J (1993) Negative regulation of G1 in mammalian cells: inhibition of cyclin E- dependent kinase by TGF-beta. Science 260: 536¨C539
Korkolopoulou P, Christodoulou P, Kouzelis K, Hadjiyannakis M, Priftis A, Stamoulis G, Seretis A and Thomas-Tsagli E (1997) MDM 2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor. Br J Cancer 75: 1269¨C1278
Kubbutat M H, Jones S N and Vousden K H (1997) Regulation of p53 stability by Mdm2. Nature 387: 299¨C303
Kuppner M C, Van Meir E, Gauthier T, Hamou M F and de Tribolet N (1992) Differential expression of the CD44 molecule in human brain tumours. Int J Cancer 50: 572¨C577
Levine A J (1997) p53, the cellular gatekeeper for growth and division. Cell 88: 323¨C331
Li H, Lochmuller H, Yong V W, Karpati G and Nalbantoglu J (1997a) Adenovirus-mediated wild-type p53 gene transfer and overexpression induces apoptosis of human glioma cells independent of endogenous p53 status. J Neuropathol Exp Neurol 56: 872--878
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S I, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner S H, Giovanella B C, Ittmann M, Tycko B, Hibshoosh H, Wigler M H and Parsons R (1997b) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [see comments]. Science 275: 1943¨C1947
Liau L M, Black K L, Prins R M, Sykes S N, DiPatre P L, Cloughesy T F, Becker D P and Bronstein J M (1999) Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg 90: 1115¨C1124
Liesi P, Dahl D and Vaheri A (1983) Laminin is produced by early rat astrocytes in primary culture. J Cell Biol 96: 920¨C924
Liotta L A (1986) Tumor invasion and metastases¨Crole of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res 46: 1¨C7
Lukashev M E and Werb Z (1998) ECM signalling: orchestrating cell behaviour and misbehaviour. Trends Cell Biol 8:437¨C441
Maltzman W and Czyzyk L (1984) UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 4: 1689¨C1694
Merchant R E, Baldwin N G, Rice C D and Bear H D (1997) Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes. Neurol Res 19: 145¨C152
Michieli P, Chedid M, Lin D, Pierce J H, Mercer W E and Givol D (1994) Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res 54: 3391¨C3395
Miyashita T and Reed J C (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293¨C299
Nagane M, Coufal F, Lin H, Bogler O, Cavenee W K and Huang H J (1996) A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res 56: 5079¨C5086
Nakano A, Tani E, Miyazaki K, Furuyama J and Matsumoto T (1993) Expressions of matrilysin and stromelysin in human glioma cells. Biochem Biophys Res Commun 192:999¨C1003
Nishikawa R, Ji X D, Harmon R C, Lazar C S, Gill G N, Cavenee W K and Huang H J (1994) A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity.Proc Natl Acad Sci U S A 91: 7727¨C7731
Nozaki M, Tada M, Matsumoto R, Sawamura Y, Abe H and Iggo R D (1998) Rare occurrence of inactivating p53 gene mutations in primary non-astrocytic tumors of the central nervous system: reappraisal by yeast functional assay. Acta Neuropathol (Berl) 95: 291¨C296
Oltvai Z N, Milliman C L and Korsmeyer S J (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609¨C619
Owen-Schaub L B, Zhang W, Cusack J C, Angelo L S, Santee S M, Fujiwara T, Roth J A, Deisseroth A B, Zhang W W,Kruzel E and et al. (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression.Mol Cell Biol 15: 3032¨C3040
Patsouris E, Davaki P, Kapranos N, Davaris P and Papageorgiou K (1996) A study of apoptosis in brain tumors by in situ end-labeling method. Clin Neuropathol 15: 337¨C341
Perrin G, Schnuriger V, Quiquerez A L, Saas P, Pannetier C, de Tribolet N, Tiercy J M, Aubry J P, Dietrich P Y and Walker P R (1999) Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset. Int Immunol 11: 1337¨C1350
Plate K H and Risau W (1995) Angiogenesis in malignant gliomas. Glia 15:339¨C347
Prigent S A, Nagane M, Lin H, Huvar I, Boss G R, Feramisco J R, Cavenee W K and Huang H S (1996) Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras- Shc-Grb2 pathway. J Biol Chem 271:25639¨C25645
Rempel S A (1998) Molecular biology of central nervous system tumors. Curr Opin Oncol 10: 179¨C185
Rempel S A, Ge S and Gutierrez J A (1999) SPARC: a potential diagnostic marker of invasive meningiomas. Clin Cancer Res 5: 237¨C241
Rempel S A, Rosenblum M L, Mikkelsen T, Yan P S, Ellis K D, Golembieski W A, Sameni M, Rozhin J, Ziegler G and Sloane B F (1994) Cathepsin B expression and localization in glioma progression and invasion. Cancer Res 54: 6027¨C6031
Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand B C, Helie M, Kleinman G, Yahanda A, Fearon E R, Kleihues P and Reale M A (1997) Loss of DCC expression and glioma progression. Cancer Res 57: 382¨C386
Romanic A M and Madri J A (1994) Extracellular matrixdegrading proteinases in the nervous system. Brain Pathol 4: 145¨C156
Sage E H (1997) Terms of attachment: SPARC and tumorigenesis [news]. Nat Med 3: 144¨C146
Sato K, Schauble B, Kleihues P and Ohgaki H (1996) Infrequent alterations of the p15, p16, CDK4 and cyclin D1 genes in non-astrocytic human brain tumors. Int J Cancer 66: 305¨C308
Sawaya R, Ramo O J, Shi M L and Mandybur G (1991) Biological significance of tissue plasminogen activator content in brain tumors. J Neurosurg 74: 480¨C486
Schlessinger J (1988) Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 13: 443¨C447
Schmidt E E, Ichimura K, Messerle K R, Goike H M and Collins V P (1997) Infrequent methylation of CDKN2 A(MTS1/p16) and rare mutation of both CDKN2 A and CDKN2B(MTS2/p15) in primary astrocytic tumours. Br J Cancer 75: 2¨C8
Schmidt E E, Ichimura K, Reifenberger G and Collins V P (1994) CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res 54: 6321¨C6324
Serrano M, Hannon G J and Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 [see comments]. Nature 366: 704¨C707
Sherman L, Sleeman J, Herrlich P and Ponta H (1994) Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 6:726¨C733
Shu H K, Kim M M, Chen P, Furman F, Julin C M and Israel M A (1998) The intrinsic radioresistance of glioblastomaderived cell lines is associated with a failure of p53 to induce p21(BAX) expression. Proc Natl Acad Sci USA 95:14453¨C14458
Stuart E T, Haffner R, Oren M and Gruss P (1995a) Loss of p53 function through PAX-mediated transcriptional repression.Embo J 14: 5638¨C5645
Stuart E T, Kioussi C, Aguzzi A and Gruss P (1995b) PAX5 expression correlates with increasing malignancy in human astrocytomas. Clin Cancer Res 1: 207¨C214
Tachibana O, Nakazawa H, Lampe J, Watanabe K, Kleihues P and Ohgaki H (1995) Expression of Fas/APO-1 during the progression of astrocytomas. Cancer Res 55: 5528¨C5530
Tada M, Iggo R D, Waridel F, Nozaki M, Matsumoto R, Sawamura Y, Shinohe Y, Ikeda J and Abe H (1997) Reappraisal of p53 mutations in human malignant astrocytic neoplasms by p53 functional assay: comparison with conventional structural analyses. Mol Carcinog 18: 171¨C176
Takano S, Yoshii Y, Kondo S, Suzuki H, Maruno T, Shirai S and Nose T (1996) Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res 56: 2185¨C2190
Tsurushima H, Liu S Q, Tsuboi K, Yoshii Y, Nose T and Ohno T (1996) Induction of human autologous cytotoxic T lymphocytes against minced tissues of glioblastoma multiforme. J Neurosurg 84: 258¨C263
Tsuzuki T, Tsunoda S, Sakaki T, Konishi N, Hiasa Y and Nakamura M (1996) Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas. Cancer 78: 287¨C293
Ueki K, Ono Y, Henson J W, Efird J T, von Deimling A and Louis D N (1996) CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56: 150¨C153
Ullrich A and Schlessinger J (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203¨C212
Van Meir E (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential to solid tumours [letter]. Neurosurgery 39: 878¨C879
Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P and Ohgaki H (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217¨C223; discussion 23¨C4
Weller M, Frei K, Groscurth P, Krammer P H, Yonekawa Y and Fontana A (1994) Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J Clin Invest 94:954¨C964
Weller M, Malipiero U, Rensing-Ehl A, Barr P J and Fontana A (1995) Fas/APO-1 gene transfer for human malignant glioma. Cancer Res 55: 2936¨C2944
White E (1996) Life, death, and the pursuit of apoptosis. Genes Dev 10: 1¨C15
Yamamoto T, Nishida T, Miyajima N, Kawai S, Ooi T and Toyoshima K (1983) The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell 35: 71¨C78
Yamasaki T, Akiyama Y, Fukuda M, Kimura Y, Moritake K,Kikuchi H, Ljunggren H G, Karre K and Klein G (1996) Natural resistance against tumors grafted into the brain in association with histocompatibility-class-I-antigen expression.Int J Cancer 67: 365¨C771
Yount G L, Haas-Kogan D A, Vidair C A, Haas M, Dewey W C and Israel M A (1996) Cell cycle synchrony unmasks the influence of p53 function on radiosensitivity of human glioblastoma cells. Cancer Res 56: 500¨C506
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Class, R. (2003). Molecular Biology. In: Petrovich, Z., Brady, L.W., Apuzzo, M.L.J., Bamberg, M. (eds) Combined Modality Therapy of Central Nervous System Tumors. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56411-6_3
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