Targeting adaptive glioblastoma: an overview of proliferation and invasion.

Glioblastoma is one of the most devastating cancers, in which tumor cell infiltration into surrounding normal brain tissue confounds clinical management. This review describes basic and translational research into glioma proliferation and invasion, in particular the phenotypic switch underlying a stochastic "go or grow" model of tumor cell behavior. We include recent progress in system genomics, cancer stem cell theory, and tumor-microenvironment interaction, from which novel therapeutic strategies may emerge for managing this malignant disease. We suggest that an effective therapeutic strategy should target both adaptive glioblastoma cells and the stroma-tumor interaction.

[1]  Irving L Weissman,et al.  Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. , 2006, Cancer research.

[2]  Daniel J Brat,et al.  Pseudopalisades in Glioblastoma Are Hypoxic, Express Extracellular Matrix Proteases, and Are Formed by an Actively Migrating Cell Population , 2004, Cancer Research.

[3]  Mohammad Kohandel,et al.  Investigating the Link between Molecular Subtypes of Glioblastoma, Epithelial-Mesenchymal Transition, and CD133 Cell Surface Protein , 2013, PloS one.

[4]  A. Guha,et al.  Targeting Metabolic Remodeling in Glioblastoma Multiforme , 2010, Oncotarget.

[5]  Paul A. Wiggins,et al.  Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state , 2011, Proceedings of the National Academy of Sciences.

[6]  Yuri Kotliarov,et al.  Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. , 2006, Cancer cell.

[7]  R. Weinberg,et al.  AACR special conference on epithelial-mesenchymal transition and cancer progression and treatment. , 2010, Cancer research.

[8]  Hui Wang,et al.  Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. , 2009, Cancer cell.

[9]  John A Butman,et al.  Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  G. V. Vande Woude,et al.  RTK inhibition: looking for the right pathways toward a miracle. , 2012, Future oncology.

[11]  B. Hempstead,et al.  The p75 Neurotrophin Receptor Is a Central Regulator of Glioma Invasion , 2007, PLoS biology.

[12]  Xiao-Fan Wang,et al.  ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses , 2001, Nature.

[13]  Tao Lu,et al.  Aberrant constitutive activation of nuclear factor κB in glioblastoma multiforme drives invasive phenotype , 2007, Journal of Neuro-Oncology.

[14]  F. Ismail-Beigi,et al.  Regulation of glut1 mRNA by Hypoxia-inducible Factor-1 , 2001, The Journal of Biological Chemistry.

[15]  Paul S Mischel,et al.  Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  E. Lengyel,et al.  Ligand independent activation of c-Met by fibronectin and α5β1-integrin regulates ovarian cancer invasion and metastasis , 2010, Oncogene.

[17]  R. Kerbel,et al.  Glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. , 2009, Cancer research.

[18]  Forest M White,et al.  Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma , 2007, Proceedings of the National Academy of Sciences.

[19]  I. Brook.  Amoxicillin–clavulante as the gold standard empirical therapy of acute bacteria rhinosinusitis , 2012, Expert review of anti-infective therapy.

[20]  L. Deangelis,et al.  Glioblastoma and other malignant gliomas: a clinical review. , 2013, JAMA.

[21]  C. Cobbs,et al.  The emerging role of MMP14 in brain tumorigenesis and future therapeutics. , 2014, Biochimica et biophysica acta.

[22]  Chuanlu Jiang,et al.  Stromal protein periostin identified as a progression associated and prognostic biomarker in glioma via inducing an invasive and proliferative phenotype. , 2013, International journal of oncology.

[23]  J. Uhm.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2009 .

[24]  K. Black,et al.  Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma , 2006, Molecular Cancer.

[25]  S. Gabriel,et al.  Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. , 2010, Cancer cell.

[26]  Erik Sahai,et al.  Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis , 2003, Nature Cell Biology.

[27]  R. Deberardinis,et al.  Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis , 2007, Proceedings of the National Academy of Sciences.

[28]  J. Eschbacher,et al.  Reciprocal Activation of Transcription Factors Underlies the Dichotomy between Proliferation and Invasion of Glioma Cells , 2013, PloS one.

[29]  R. Nishikawa,et al.  ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion. , 2007, Cancer research.

[30]  H. Friedman,et al.  Temozolomide and treatment of malignant glioma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  B. Cochran,et al.  STAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells , 2009, Stem cells.

[32]  F. Marincola,et al.  Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma , 2011, Proceedings of the National Academy of Sciences.

[33]  R. Gillies,et al.  Why do cancers have high aerobic glycolysis? , 2004, Nature Reviews Cancer.

[34]  P. Wen.  American Society of Clinical Oncology 2010: report of selected studies from the CNS tumors section , 2010, Expert review of anticancer therapy.

[35]  J. Rich,et al.  Potential therapeutic implications of cancer stem cells in glioblastoma. , 2010, Biochemical pharmacology.

[36]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Hong Peng,et al.  Interactions between cancer stem cells and their niche govern metastatic colonization , 2011, Nature.

[38]  S. Weiss,et al.  Proliferation of Human Glioblastoma Stem Cells Occurs Independently of Exogenous Mitogens , 2009, Stem cells.

[39]  M. Sabel,et al.  Glioblastoma multiforme metastasis outside the CNS: three case reports and possible mechanisms of escape. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  S. Leibler,et al.  Phenotypic Diversity, Population Growth, and Information in Fluctuating Environments , 2005, Science.

[41]  Zang Ai-hua,et al.  Stem Cells,Cancer and Cancer Stem Cells , 2005 .

[42]  T. Golub,et al.  Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion , 2012, Nature.

[43]  L. Cantley,et al.  Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation , 2009, Science.

[44]  Daniel J Brat,et al.  Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma , 2004, Laboratory Investigation.

[45]  William Pao,et al.  MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib , 2007, Proceedings of the National Academy of Sciences.

[46]  N. Denko,et al.  HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. , 2006, Cell metabolism.

[47]  P. Kleihues,et al.  IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. , 2009, The American journal of pathology.

[48]  Q. Shi,et al.  Bex2 Controls Proliferation of Human Glioblastoma Cells Through NF-κB Signaling Pathway , 2014, Journal of Molecular Neuroscience.

[49]  B. Neyns,et al.  Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[50]  K. Aldape,et al.  Epidermal Growth Factor (EGF)-enhanced Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression Promotes Macrophage and Glioblastoma Cell Interaction and Tumor Cell Invasion* , 2013, The Journal of Biological Chemistry.

[51]  J. Willey,et al.  Molecular Cancer Stable Low-level Expression of P21 Waf1/cip1 in A549 Human Bronchogenic Carcinoma Cell Line-derived Clones Down-regulates E2f1 Mrna and Restores Cell Proliferation Control , 2006 .

[52]  Ping Zhao,et al.  A highly invasive human glioblastoma pre-clinical model for testing therapeutics , 2008, Journal of Translational Medicine.

[53]  R. McLendon,et al.  Erythropoietin Receptor Signaling Through STAT3 Is Required For Glioma Stem Cell Maintenance. , 2010, Genes & cancer.

[54]  D. Steindler,et al.  Chondroitin Sulfate Proteoglycans Potently Inhibit Invasion and Serve as a Central Organizer of the Brain Tumor Microenvironment , 2013, The Journal of Neuroscience.

[55]  W. Birchmeier,et al.  Targeting MET in cancer: rationale and progress , 2012, Nature Reviews Cancer.

[56]  J. Mandel,et al.  Update on Anti-angiogenic Treatment for Malignant Gliomas , 2014, Current Oncology Reports.

[57]  Rebecca A Betensky,et al.  Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. , 2011, Cancer cell.

[58]  G. V. Vande Woude,et al.  Novel Therapeutic Inhibitors of the c-Met Signaling Pathway in Cancer , 2009, Clinical Cancer Research.

[59]  Cynthia Hawkins,et al.  Identification of a cancer stem cell in human brain tumors. , 2003, Cancer research.

[60]  Gabriele Bergers,et al.  Modes of resistance to anti-angiogenic therapy , 2008, Nature Reviews Cancer.

[61]  Nariyoshi Shinomiya,et al.  Proliferation and invasion: plasticity in tumor cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[62]  S. Gautam,et al.  The natural history of extracranial metastasis from glioblastoma multiforme , 2011, Journal of Neuro-Oncology.

[63]  Jane Fridlyand,et al.  Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors , 2012, Nature.

[64]  Peter Canoll,et al.  Transplanted glioma cells migrate and proliferate on host brain vasculature: A dynamic analysis , 2006, Glia.

[65]  H. Zentgraf,et al.  Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors , 2010, Brain pathology.

[66]  D. Cheresh,et al.  VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. , 2012, Cancer cell.

[67]  R. Kerbel,et al.  Tumor and Host-Mediated Pathways of Resistance and Disease Progression in Response to Antiangiogenic Therapy , 2009, Clinical Cancer Research.

[68]  D. Haussler,et al.  The Somatic Genomic Landscape of Glioblastoma , 2013, Cell.

[69]  D. Steindler,et al.  The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance , 2013, EMBO molecular medicine.

[70]  R. Graham,et al.  Extracranial glioblastoma in transplant recipients , 2014, Journal of Cancer Research and Clinical Oncology.

[71]  J. Uhm,et al.  The transcriptional network for mesenchymal transformation of brain tumours , 2010 .

[72]  Qiulian Wu,et al.  Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. , 2006, Cancer research.

[73]  M. Westphal,et al.  Cost of migration: invasion of malignant gliomas and implications for treatment. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  Alejandra Bruna,et al.  High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. , 2007, Cancer cell.

[75]  M. Prados,et al.  Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. , 2004, International journal of radiation oncology, biology, physics.

[76]  Mitchel S Berger,et al.  Neural stem cells and the origin of gliomas. , 2005, The New England journal of medicine.

[77]  E. T. Gawlinski,et al.  Acid-mediated tumor invasion: a multidisciplinary study. , 2006, Cancer research.

[78]  G. Fuller,et al.  Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice , 2010, Neuro-oncology.

[79]  M. Weller,et al.  Angiogenesis inhibition for glioblastoma at the edge: beyond AVAGlio and RTOG 0825. , 2013, Neuro-oncology.

[80]  G. V. Vande Woude,et al.  Showering c-MET-dependent cancers with drugs. , 2008, Current opinion in genetics & development.

[81]  R. Weinberg,et al.  Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits , 2009, Nature Reviews Cancer.

[82]  T. Mikkelsen,et al.  Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[83]  Eric C. Holland,et al.  Gliomagenesis: genetic alterations and mouse models , 2001, Nature Reviews Genetics.

[84]  Thomas D. Wu,et al.  Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. , 2006, Cancer cell.

[85]  M. Pomper,et al.  EGFRvIII and c-Met pathway inhibitors synergize against PTEN-null/EGFRvIII+ glioblastoma xenografts , 2009, Molecular Cancer Therapeutics.

[86]  J. Shao,et al.  Elevated expressions of survivin and VEGF protein are strong independent predictors of survival in advanced nasopharyngeal carcinoma , 2008, Journal of Translational Medicine.

[87]  M. Caligiuri,et al.  A cell initiating human acute myeloid leukaemia after transplantation into SCID mice , 1994, Nature.

[88]  Luca Toschi,et al.  Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. , 2010, Cancer cell.

[89]  K. Schaller,et al.  Identification of intrinsic in vitro cellular mechanisms for glioma invasion. , 2011, Journal of theoretical biology.

[90]  Thomas S Deisboeck,et al.  Evolutionary game theory in an agent-based brain tumor model: exploring the 'Genotype-Phenotype' link. , 2006, Journal of theoretical biology.

[91]  E. Hudson,et al.  Met and hepatocyte growth factor/scatter factor expression in human gliomas. , 1997, Cancer research.

[92]  Susan M. Chang,et al.  A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. , 2010, Neuro-oncology.

[93]  Michael C. Ostrowski,et al.  MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. , 2010, Molecular cell.

[94]  Mark W. Dewhirst,et al.  Glioma stem cells promote radioresistance by preferential activation of the DNA damage response , 2006, Nature.

[95]  A. Verma.  MGMT Gene Silencing and Benefit From Temozolomide in Glioblastoma , 2006 .

[96]  J. Uhm.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2009 .