title: Functional assessment of glioma pathogenesis by in vivo multi-parametric magnetic resonance imaging and in vitro analyses.
abstract: Gliomas are aggressive brain tumors with poor prognosis. In this study, we report a novel approach combining both in vivo multi-parametric MRI and in vitro cell culture assessments to evaluate the pathogenic development of gliomas. Osteopontin (OPN), a pleiotropic factor, has been implicated in the formation and progression of various human cancers, including gliomas, through its functions in regulating cell proliferation, survival, angiogenesis, and migration. Using rat C6 glioma model, the combined approach successfully monitors the acquisition and decrease of cancer hallmarks. We show that knockdown of the expression of OPN reduces C6 cell proliferation, survival, viability and clonogenicity in vitro, and reduces tumor burden and prolongs animal survival in syngeneic rats. OPN depletion is associated with reduced tumor growth, decreased angiogenesis, and an increase of tumor-associated metabolites, as revealed by T2-weighted images, diffusion-weighted images, K(trans) maps, and 1H-MRS, respectively. These strategies allow us to define an important role of OPN in conferring cancer hallmarks, which can be further applied to assess the functional roles of other candidate genes in glioma. In particular, the non-invasive multi-parametric MRI measurement of cancer hallmarks related to proliferation, angiogenesis and altered metabolism may serve as a useful tool for diagnosis and for patient management.
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.|Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan.
authors.forename: Nai-Wei
authors.initials: NW
authors.lastname: Yao
authors.affiliation: Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan.
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan.
authors.forename: Hsiu-Ting
authors.initials: HT
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Tung
authors.initials: CT
authors.lastname: Yen
authors.affiliation: Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan.|Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jeou-Yuan
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002470:Cell Survival; D004195:Disease Models, Animal; D005910:Glioma / Q000175:diagnosis*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C506897:Spp1 protein, rat; D053495:Osteopontin