The Tumor Microenvironment

  • Lissa Baird
  • Alexey Terskikh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 671)


Recent advances in stem cell and developmental neurobiology have uncovered new perspectives from which we investigate various forms of cancer. Specifically, the hypothesis that tumors are comprised of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the cancer stem cell hypothesis. The region where this is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorgenesis. Evidence of brain tumor stem cells will be reviewed along with the role of tumor environment as the context within which these cells should be understood.


Stem Cell Cancer Stem Cell Tumor Microenvironment Neural Stem Cell Tumor Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Mabon R, Svien H, Adson A et al. Astrocytomas of the cerebellum. Arch Neurol Psychiatry 1950; 64(1):74–88.PubMedGoogle Scholar
  2. 2.
    Doetsch F, Caillé I, Lim D et al. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97(6):703–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Sakariassen P, Immervoll H, Chekenya M. Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 2007; 9(11):882–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Huntly B, Gilliland D. Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005; 5(4):311–21.CrossRefPubMedGoogle Scholar
  5. 5.
    Clarke M, Dick J, Dirks P et al. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66(19):9339–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Lee J, Herlyn M. Old disease, new culprit: tumor stem cells in cancer. J Cell Physiol 2007; 213(3):603–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Buzzeo M, Scott E, Cogle C. The hunt for cancer-initiating cells: a history stemming from leukemia. Leukemia 2007; 21(8):1619–27.CrossRefPubMedGoogle Scholar
  8. 8.
    Lapidot T, Sirard C, Vormoor J et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367(6464):645–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Al-Hajj M, Wicha M, Benito-Hernandez A et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7):3983–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Ignatova T, Kukekov V, Laywell E et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 2002; 39(3):193–206.CrossRefPubMedGoogle Scholar
  11. 11.
    Vescovi A, Galli R, Reynolds B. Brain tumour stem cells. Nat Rev Cancer 2006; 6(6):425–36.CrossRefPubMedGoogle Scholar
  12. 12.
    Singh S, Hawkins C, Clarke I et al. Identification of human brain tumour initiating cells. Nature 2004; 432(7015):396–401.CrossRefPubMedGoogle Scholar
  13. 13.
    Taylor M, Poppleton H, Fuller C et al. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 2005; 8(4):323–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Merkle F, Tramontin A, García-Verdugo J et al. Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci USA 2004; 101(50):17528–32.CrossRefPubMedGoogle Scholar
  15. 15.
    Stupp R, Hegi M. Targeting brain-tumor stem cells. Nat Biotechnol 2007; 25(2):193–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Bao S, Wu Q, McLendon R et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444(7120):756–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Hill R. Identifying cancer stem cells in solid tumors: case not proven. Cancer Res 2006; 15;66(4):1883–90; discussion 1895-6.Google Scholar
  18. 18.
    Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004; 116(6):769–78.CrossRefPubMedGoogle Scholar
  19. 19.
    Ailles L, Weissman I. Cancer stem cells in solid tumors. Curr Opin Biotechnol 2007; 18(5):460–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Kenny P, Lee G, Bissell M. Targeting the tumor microenvironment. Front Biosci 2007; 12:3468–74.CrossRefPubMedGoogle Scholar
  21. 21.
    Egeblad M, Littlepage L, Werb Z. The fibroblastic coconspirator in cancer progression. Cold Spring Harb Symp Quant Biol 2005; 70:383–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Ishiguro K, Yoshida T, Yagishita H et al. Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas. Gut 2006; 55(5):695–702.CrossRefPubMedGoogle Scholar
  23. 23.
    Weber F, Shen L, Fukino K et al. Total-genome analysis of BRCA1/2-related invasive carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation. Am J Hum Genet 2006; 78(6):961–72.CrossRefPubMedGoogle Scholar
  24. 24.
    Kim B, Li C, Qiao W et al. Smad4 signalling in T-cells is required for suppression of gastrointestinal cancer. Nature 2006; 441(7096):1015–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Calabrese C, Poppleton H, Kocak M et al. A perivascular niche for brain tumor stem cells. Cancer Cell 2007; 11(1):69–82.CrossRefPubMedGoogle Scholar
  26. 26.
    Piccirillo S, Reynolds B, Zanetti N et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 2006; 444(7120):761–5.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Division of NeurosurgeryUCSD Medical CenterSan DiegoUSA
  2. 2.Del E. Webb Neuroscience, Aging and Stem Cell Research CenterBurnham Institute for Regenerative MedicineLa JollaUSA

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