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Matrix or
            Cells         Tumor type     Condition     Experiment        scaffold   Effect              Ref.
                                                                                    Tumor cell-derived
                                                       Quantification of            VEGF-A promotes
                                         3D, transwell   VEGE-A induced,            medulloblastoma cell
            DAOY, UW228   Medulloblastoma                                Matrigel                       [97]
                                         migration     PERK-dependent               migration and invasion
                                                       transwell migration.         through VEGFR2 and
                                                                                    enhanced by PERK.
                                                       Quantification of
                                                       EphB1 effect on SHH          Knockdown of Eph-B1
                                                       medulloblastoma
                                         3D, transwell                              causes reduction in B-1
            DAOY, UW228   Medulloblastoma              transwell migration   None                       [98]
                                         migration                                  integrin expression and in
                                                       using electrical             growth and migration.
                                                       impedance
                                                       measurements.
                                                       Quantitative and             Matrigel invasion of MB
                                         3D, µLane     qualitative analysis of      cells towards an EGF
            DAOY          Medulloblastoma  microfluidics   chemotactic response   Matrigel  gradient is blocked by   [99]
                                         system        of MB cells to a             pharmacological PI3-K
                                                       gradient of EGF in a         inhibition.
                                                       microfluidic system.
                                                                                    PDGF signaling restricts
                                         3D, transwell   Quantitative analysis      expression of negative
                                         migration,    of PDGFR control
            DAOY          Medulloblastoma                                Matrigel   regulator GRK6 and   [100]
                                         xCelligence   of CXCR4 pro-                promotes CXCR4-Src-
                                         assay         migratory signaling          dependent cell migration.
                                                       in SHH MB model.

                                                       Quantification of
            DAOY, UW228-                 3D confrontation                           Slit represses MB
            3             Medulloblastoma  co-culture  repulsive action of   Collagen I  invasion in collagen gels.   [101]
                                                       Slit-Robo signaling
                                                       during MB invasion.
                                                                                    SPARC suppresses
                                                       Evaluation of impact         migration and invasion
                                                       of matricellular             by repressing Rho-
                                         2D/3D transwell
            DAOY          Medulloblastoma              SPAR on MB cell   Matrigel   GTPase activation   [45]
                                         migration
                                                       migration and                and by triggering Src-
                                                       invasion                     dependent cytoskeleton
                                                                                    reorganization.
                                                       Comparison of                Highly self-renewing
                                                       invasion and self-           CD271 high, CD133
                                                       renewal. Analysis            low MB cell population
                                                       of higher versus             in the core sustains
                                         2D spheroid
                                         outgrowth,    lower self-renewing          tumorigenesis.
            DAOY, D283    Medulloblastoma              tumor spheres and   Collagen I  Commitment to    [102]
                                         3D transwell
                                         migration     stationary versus            migration/invasion
                                                       migrating adherent           (metastatic phenotype)
                                                       MB cells with respect        is identified by reduced
                                                       to CD271 and CD133           CD271 and increased
                                                       expression.                  CD133 signature.
           Overview of a selection of primary brain tumor studies that used 3D cell culture technologies. Ara-C: cytosine β-D-arabinofuranoside;
           CXCR4: CXC-motif-chemokine receptor 4; PERK: pancreatic endoplasmic reticulum kinase; EGF: epidermal growth factor; GBM:
           glioblastoma multiforme; GM-CSF: granulocyte-macrophage colony stimulating factor; GSCs: glioblastoma stem cells; GRK6:
           g-protein coupled receptor kinase 6; HA: hyaluronic acid; HAMA: methacrylated HA; HGF: hepatocyte growth factor; IDH1: isocitrate
           dehydrogenase 1; IFO: ifosfamide; MB: medulloblastoma; MMP: matrix metalloproteinase; PEG: polyethylene glycol; PDGFR:
           platelet-derived growth factor receptor; PI3-K: phosphoinositide 3’Kinase; RGD: l-arginine, glycine, and L-aspartic acid; SAHA:
           suberoylanilide hydroxamic acid (or vorinostat a HDACi); SPARC: secreted protein acidic and rich in cysteine; Src: rous sarcoma
           kinase; TMZ: temozolomide; VEGF: vasculature endothelial growth factor; 2D/3D: two dimensional/three dimensional

           model  system:  the  system  should  mimic  biophysical  and   cytokines, metabolites) in a well controllable  manner,
           chemical properties of the tissue environment (composition   the cells should be observable to increase output options
           and stiffness of matrix,  availability  of growth factors,   (morphological analysis, use of fluorescent protein and dye
                                                                                                     [53]
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                                                                                                                         Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ May 18, 2016 ¦
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