Distinctive parameters of action of stem cells and modulatory microenvironmental microcirculation in gliomagenesis


Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.

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M. Agius, L. (2013) Distinctive parameters of action of stem cells and modulatory microenvironmental microcirculation in gliomagenesis. Stem Cell Discovery, 3, 1-6. doi: 10.4236/scd.2013.31001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Bazzoli, E., Pulvirenti, T., Oberstedt, M.C., Perna, F., Wee, B., Schultz, N., et al. (2012) MEF promotes stemness in the pathogenesis of glioma cell. Stem Cell, 11, 836-844. doi:10.1016/j.stem.2012.09.012
[2] Tan, J., Meng, Y., Huang, S. and Wang, P. (2012) Therapeutic gene products delivery by neuron stem cells. Current Pharmaceutical Biotechnology, 13, 2427-2431. doi:10.2174/138920112803341806
[3] Kong, B.H., Park, N.R., Shim, J.K., Kim, B.K., Shin, H.J., Lee, J.H., et al. (2012) Isolation of glioma cancer stem cells in relation to histological grades in glioma specimens. Child’s Nervous System, 10 November 2012. doi:10.1007/s00381-012-1964-9
[4] Ho, I.A., Toh, H.C., Ng, W.H., Teo, Y.L., Guo, C.M., Hul, K.M., et al. () Human Bone-marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesis. Stem Cells, 31, 146-155.
[5] Ueda, Y., Wei, F.Y., Hide, T., Michiue, H., Takayama, K., Kaitsuka, T., Nakamura, H., et al. (2012) Induction of autophagic cell death of glioma-initiating cells by cellpenetrating d-isomer peptides consisting of Pas and the p53C-terminus. Biomaterials, 33, 9061-9069. doi:10.1016/j.biomaterials.2012.09.003
[6] Zou, Y., Niu, W., Qin, S., Downes, M., Burns, D.K. and Zhang, C.L. (2012) The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche. Molecular and Cellular Biology, 32, 4811-4820. doi:10.1128/MCB.01122-12
[7] Lee da, Y., Gianino, S.M. and Gutmann, D.H. (2012) Innate neural stem cell heterogeneity determines the patterning of glioma formation in children. Cancer Cell, 22, 131-138. doi:10.1016/j.ccr.2012.05.036
[8] Wu, N., Xiao, L., Zhao, X., Zhao, J., Wang, J., Wang, F., et al. (2012) MiR-125b regulates the proliferation of glioblastoma stem cells by targeting E2F2. FEBs Letters, 586, 3831-3839.
[9] de Alucida Sassi, F., Lunardi Brunetto, A., Schwartsmann, G., Roesler, R. and Abujamra, A.L. (2012) Glioma revisited: From neurogenesis and cancer stem cells to the epigenetic regulation of the niche. Journal of Oncology, 2012, 537861.
[10] Kim, S.M., Woo, J.S., Jeong, C.H., Ryu, C.H., Lim, J.Y. and Jeun, S.S. (2012) Effective combination therapy for malignant glioma with TRAIL-secreting mesenchymal stem cells and Lipoxygenase Inhibitor MK886. Cancer Research, 72, 4807-4817. doi:10.1158/0008-5472.CAN-12-0123
[11] Dokic, I., Hartmann, C., Herold-Mende, C. and Regnier-Vigouroux, A. (2012) Glutathione peroxidase 1 activity dictates the sensitivity of glioblastoma cells to oxidative stress. Glia, 60, 1785-800. doi:10.1002/glia.22397
[12] Kim, H.S., Woolard, K., Lai, C., Bauer, P.O., Maric, D., Song, H., et al. (2012) Gliomagenesis arising from Ptenand Ink 4a/Arf-deficient neural progenitor cells is mediated by the p53-Fbxw 7/Cdc4 pathway, which controls c-Myc. Cancer Research, 72, 6065-6075. doi:10.1158/0008-5472.CAN-12-2594
[13] Gopisetty, G., Xu, J., Sampath, D., Colman, H. and Puduvalli, V.K. (2012) Epigenetic regulation of CD133/PROM 1 expression in glioma stem cells by Sp1/myc and promoter methylation. Oncogene, 3 September 2012.
[14] Charles, N.A., Holland, E.C., Gilbertson, R., Glass, R. and Kettenmann, H. The brain tumor microenvironment. Glia, 60, 502-514.
[15] Lima, F.R., Kahn, S.A., Soletti, R.C., Biasoli, D., Alves, T., daFonseca, A.C., et al. (2012) Glioblastoma: Therapeutic challenges, what lies ahead. Biochimica et Biophysica Acta, 1826, 338-349.
[16] Cruz, M.H., Siden, A., Calaf, G.M., Delwar, Z.M., Yakisich, J.S. (2012) The stemness phenotype model. ISRN Oncology, 2012, 392647.
[17] Chan, X.H., Nama, S., Gopal, F., Rizk, P., Ramasamy, S., Sundarain, G., et al., Targeting glioma stem cells by functional inhibition of a Prosurvival OncomiR-138 in malignant gliomas. Cell Reports, 2, 591-602. doi:10.1016/j.celrep.2012.07.012
[18] Speranza, M.C., Frattini, V., Pisati, F., Kapetis, D., Porrati, P., Eoli, M., et al. (2012) NEDD9, a novel target of miR-145, increases the invasiveness of glioblastoma. Oncotarget, 3, 123-134.
[19] Dong, Y., Han, Q., Zou, Y., Deng, Z., Lu, X., Wang, X., et al. (2012) Long-term expsure to imatinib reduced cancer stem cell ability through induction of cell differentiation via activation of MAPK signalling in glioblastoma cells. Molecular and Cellular Biochemistry, 370, 89-102. doi:10.1007/s11010-012-1401-0
[20] Jiang, Y. and Uhrborn, L. (2012) On the origin of glioma. Upsala Journal of Medical Sciences, 117, 113-121. doi:10.3109/03009734.2012.658976
[21] Chen, J., Li, Y., Yu, T.S., McKay, R.M., Burns, D.K., Kernie, S.G., et al. (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature, 488, 522-526. doi:10.1038/nature11287
[22] Mazzoleni, S. and Galli, R. (2012) Gliomagenesis: A game played by few players or a team effort. Frontiers in Bioscience, 4, 205-213.
[23] Zhu, V.F., Yang, J., Lebrun, D.G. and Li, M. (2012) Understanding the role of cytokines in glioblastoma multiforme pathogenesis. Cancer Letters, 316, 139-150. doi:10.1016/j.canlet.2011.11.001
[24] Bulnes, S., Bengoetxea, H., Ortuza, N., Argandona, E.G., Garcia-Blanco, A., Rico-Barrio, I., et al. (2012) Angiogenic signalling pathways atered in gliomas; selection mechanisms for more aggressive neoplastic subpopulations with invasive phenotype. Journal of Signal Transduction, 2012, 597915.
[25] Sampetrean, O., Saga, I., Nakanishi, M., Sugihara, E., Fukaya, R., Onishi, N., et al. (2011) Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells. Neoplasia, 13, 784-791.
[26] Panciani, P.F., Fontanella, M., Tamagno, I., Battaglia, L., Garbossa, D., Inghirami, G., et al. (2012) Stem cells based therapy in high grade glioma: Why the intraventricular route should be preferred? Journal of Neurosurgical Sciences, 56, 221-229.
[27] Ghazi, S.O., Stark, M., Zhao, Z., Mobley, B.C., Munden, A., Hover, L., et al. (2012) Cell of origin determines tumor phenotype in an oncogenic Ras/p53 knockout transgenic model of high grade glioma. Journal of Neuropathology & Experimental Neurology, 71, 729040. doi:10.1097/NEN.0b013e3182625c02
[28] Phuphanich, S., Wheeler, C.J., Rudnick, J.D., Mazer, M., Wang, H., Nuno, M.A., et al. (2012) Phase 1 Trial of a multiepitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunology, Immunotherapy, Epub Ahead of Print. doi:10.1007/s00262-012-1319-0
[29] Velpula, K.K., Rehman, A.A., Chelluboina, B., Dasari, V.R., Gondi, C.S., Rao, J.S., et al. (2012) Glioma stem cell invasion through regulation of the interconnected ERK, integrin alpha6 and N-cadherin signalling pathway. Cell Signal, 24, 2076-2084. doi:10.1016/j.cellsig.2012.07.002
[30] Ye, X.Z., Xu, S.L., Xin, Y.H., Yu, S.C., Ping, Y.F., Chen, L., et al. (2012) Tumor associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-Beta1 Signaling pathway. Journal of Immunology, 189, 444-453. doi:10.4049/jimmunol.1103248
[31] Florio, T. and Barbieri, F. (2012) The status of the art of human malignant glioma management: the promising role of targeting tumor-initiating cells. Drug Discovery Today, 17, 1103-1110 doi:10.1016/j.drudis.2012.06.001
[32] Kim, Y., Kim, E., Wu, Q., Guryanova, O., Hitomi, M., Lathia, J.D., et al. (2012) Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity. Genes Development, 26, 1247-1262. doi:10.1101/gad.193565.112
[33] Katsushima, K., Shinjo, K., Natsume, A., Ohka, F., Fujii, M., Osada, H., et al. (2012) Contribution of microRNA-1275 to Claudin 11 protein suppression via a polycombmediated silencing mechanism in human glioma stem-like cells. The Journal of Biological Chemistry, 287, 27396-27406. doi:10.1074/jbc.M112.359109
[34] Brescia, P., Richichi, C. and Pelicci, G. (2012) Current strategies for identification of glioma stem cells: Adequate or unsatisfactory? Journal of Oncology, 2012, 376894.

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