Pituitary Adenoma Stem Cells

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 568)

Summary

The identification of a subpopulation of brain tumor cells with potent tumorigenic capacity strengthens the cancer stem cell hypothesis of the origin of the tumors that has recently attracted the attention of many researchers. Reports have been published on the identification of tumor cells with stem cells characteristics in different types of tumors (acute myelogenic leukemia, breast cancer, prostate cancer, bone sarcomas, liver cancer, and melanomas). We and other groups have previously reported the isolation of cancer stem cells from adult glioblastoma multiforme. These cells express stem cell markers, and when differentiated they express glial and neuronal markers. In vivo they give a tumor that recapitulates the characteristics of the tumor in the patient. More recently we have isolated tumor stem-like cells also from benign tumors like pituitary adenomas. Cells derived from pituitary adenomas are able to grow as floating aggregates resembling the neurospheres (typical of normal stem cells) in a medium supplemented by growth factors (EGF and bFGF). The immunocytochemical analysis revealed that pituitary tumor stem-like cells are positives for nestin and, when grown for ten days in differentiation medium they express GFAP, BIII tubulin, and S-100. In vitro tumor stem-like cells derived from a patient with a somatotroph adenoma showed high production of growth hormone and prolactin, while cells derived from the same patient but grown in presence of fetal bovine serum showed no production of hormones.

Key words

Pituitary adenoma Tumor stem cells Epidermal growth factor Basic fibroblast growth factor Growth hormone Prolactin 

References

  1. 1.
    Laws, E.R., Jane, J.A. Jr. (2001) Pituitary tumors – long term outcomes and expectations. Clin. Neurosurg. 48, 306–319.Google Scholar
  2. 2.
    Levy, A. (2004) Pituitary disease: presentation, diagnosis, and management. J. Neurol. Neurosurg. Psychiatry 75, 47–52.CrossRefGoogle Scholar
  3. 3.
    Greenman, Y. and Melmed, S. (1996) Diagnosis and management of nonfunctioning pituitary tumors. Annu. Rev. Med. 47, 95–106.PubMedCrossRefGoogle Scholar
  4. 4.
    Melmed, S. (2003) Mechanisms for pituitary tumorigenesis: the plastic pituitary. J. Clin. Invest. 112, 1603–18.PubMedGoogle Scholar
  5. 5.
    Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., Dirks, P.B. (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821–5828.PubMedGoogle Scholar
  6. 6.
    Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., Dirks, P.B. (2004) Identification of human brain tumour initiating cells. Nature 432, 396–401.PubMedCrossRefGoogle Scholar
  7. 7.
    Hemmati, H.D., Nakano, I., Lazareff, J.A., Masterman-Smith, M., Geschwind, D.H., Bronner-Fraser, M., Kornblum, H.I. (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc. Natl. Acad. Sci. USA 100, 15178–15183.PubMedCrossRefGoogle Scholar
  8. 8.
    Polyak, K. and Hahn, W.C. (2005) Roots and stems: stem cells in cancer. Nature Medicine 11, 296–300.Google Scholar
  9. 9.
    Yuan, X., Curtin, J., Xiong, Y., Liu, G., Waschsmann-Hogiu, S., Farkas, D.L., Black, K.L., Yu, J.S. (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23, 9392–9400.PubMedCrossRefGoogle Scholar
  10. 10.
    Horvath, E., Kovacs, K. (2002) Folliculo-stellate cells of the human pituitary: a type of adult stem cell? Ultrastruct. Pathol. 26, 219–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Giometto, B., Miotto, D., Botteri, M., Alessio, L., Scanarini, M., An, S.F., Tavolato, B. (1997) Folliculo-stellate cells of human pituitary adenomas: immunohistochemical study of the monocyte/macrophage phenotype expression. Neuroendocrinology 65, 47–52.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Maxine Dunitz Neurosurgical InstituteLos AngelesUSA

Personalised recommendations