Abstract
Current literature provides significant evidence to support the concept that there are limited subpopulations of cells within a solid tumour that have increased tumour-initiating potential relative to the total tumour population. Such tumour-initiating cells have been identified in leukaemia and in a variety of solid tumours using different combinations of cell surface markers, suggesting that a tumour-initiating cell heterogeneity exists for each specific tumour. These studies have been extended to endometrial cancer; and herein we present several experimental approaches, both in vitro and in vivo, that can be used to determine whether such populations exist, and if so, to characterize them. These methods are adaptable to the investigation of tumour-initiating cells from other tumour types.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Dalerba, P., Cho, R. W., and Clarke, M. F. (2007) Cancer stem cells: models and concepts, Annu Rev Med 58, 267–284.
Kelly, P. N., Dakic, A., Adams, J. M., Nutt, S. L., and Strasser, A. (2007) Tumor growth need not be driven by rare cancer stem cells, Science 317, 337.
Friel, A. M., Sergent, P. A., Patnaude, C., Szotek, P. P., Oliva, E., Scadden, D. T., Seiden, M. V., Foster, R., and Rueda, B. R. (2008) Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells, Cell Cycle 7, 242–249.
Haraguchi, N., Utsunomiya, T., Inoue, H., Tanaka, F., Mimori, K., Barnard, G. F., and Mori, M. (2006) Characterization of a side population of cancer cells from human gastrointestinal system, Stem Cells 24, 506–513.
Patrawala, L., Calhoun, T., Schneider-Broussard, R., Zhou, J., Claypool, K., and Tang, D. G. (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2− cancer cells are similarly tumorigenic, Cancer Res 65, 6207–6219.
Szotek, P. P., Pieretti-Vanmarcke, R., Masiakos, P. T., Dinulescu, D. M., Connolly, D., Foster, R., Dombkowski, D., Preffer, F., Maclaughlin, D. T., and Donahoe, P. K. (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness, Proc Natl Acad Sci U S A 103, 11154–11159.
Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., and Clarke, M. F. (2003) Prospective identification of tumorigenic breast cancer cells, Proc Natl Acad Sci U S A 100, 3983–3988.
Singh, S. K., Hawkins, C., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., Henkelman, R. M., Cusimano, M. D., and Dirks, P. B. (2004) Identification of human brain tumour initiating cells, Nature 432, 396–401.
Ricci-Vitiani, L., Lombardi, D. G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., and De Maria, R. (2007) Identification and expansion of human colon-cancer-initiating cells, Nature 445, 111–115.
Zhang, S., Balch, C., Chan, M. W., Lai, H. C., Matei, D., Schilder, J. M., Yan, P. S., Huang, T. H., and Nephew, K. P. (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors, Cancer Res 68, 4311–4320.
Baba, T., Convery, P. A., Matsumura, N., Whitaker, R. S., Kondoh, E., Perry, T., Huang, Z., Bentley, R. C., Mori, S., Fujii, S., Marks, J. R., Berchuck, A., and Murphy, S. K. (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells, Oncogene 28, 209–218.
Curley, M. D., Therrien, V. A., Cummings, C. L., Sergent, P. A., Koulouris, C. R., Friel, A. M., Roberts, D. J., Seiden, M. V., Scadden, D. T., Rueda, B. R., and Foster, R. (2009) CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer, Stem Cells 27(12), 2875–2883.
Rutella, S., Bonanno, G., Procoli, A., Mariotti, A., Corallo, M., Prisco, M. G., Eramo, A., Napoletano, C., Gallo, D., Perillo, A., Nuti, M., Pierelli, L., Testa, U., Scambia, G., and Ferrandina, G. (2009) Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors, Clin Cancer Res 15, 4299–4311.
Hubbard, S. A., Friel, A. M., Kumar, B., Zhang, L., Rueda, B. R., and Gargett, C. E. (2009) Evidence for cancer stem cells in human endometrial carcinoma, Cancer Res 69, 8241–8248.
Bansal, N., Yendluri, V., and Wenham, R. M. (2009) The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies, Cancer Control 16, 8–13.
Eliane, J. P., Repollet, M., Luker, K. E., Brown, M., Rae, J. M., Dontu, G., Schott, A. F., Wicha, M., Doyle, G. V., Hayes, D. F., and Luker, G. D. (2008) Monitoring serial changes in circulating human breast cancer cells in murine xenograft models, Cancer Res 68, 5529–5532.
Rago, C., Huso, D. L., Diehl, F., Karim, B., Liu, G., Papadopoulos, N., Samuels, Y., Velculescu, V. E., Vogelstein, B., Kinzler, K. W., and Diaz, L. A., Jr. (2007) Serial assessment of human tumor burdens in mice by the analysis of circulating DNA, Cancer Res 67, 9364–9370.
Yin, A. H., Miraglia, S., Zanjani, E. D., Almeida-Porada, G., Ogawa, M., Leary, A. G., Olweus, J., Kearney, J., and Buck, D. W. (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells, Blood 90, 5002–5012.
Miraglia, S., Godfrey, W., Yin, A. H., Atkins, K., Warnke, R., Holden, J. T., Bray, R. A., Waller, E. K., and Buck, D. W. (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning, Blood 90, 5013–5021.
Collins, A. T., Berry, P. A., Hyde, C., Stower, M. J., and Maitland, N. J. (2005) Prospective identification of tumorigenic prostate cancer stem cells, Cancer Res 65, 10946–10951.
Lane, S. W., Scadden, D. T., and Gilliland, D. G. (2009) The leukemic stem cell niche: current concepts and therapeutic opportunities, Blood 114, 1150–1157.
Iwasaki, H., and Suda, T. (2009) Cancer stem cells and their niche, Cancer Sci 100, 1166–1172.
Meads, M. B., Hazlehurst, L. A., and Dalton, W. S. (2008) The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance, Clin Cancer Res 14, 2519–2526.
Adams, G. B., Chabner, K. T., Alley, I. R., Olson, D. P., Szczepiorkowski, Z. M., Poznansky, M. C., Kos, C. H., Pollak, M. R., Brown, E. M., and Scadden, D. T. (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor, Nature 439, 599–603.
Mayack, S. R., and Wagers, A. J. (2008) Osteolineage niche cells initiate hematopoietic stem cell mobilization, Blood 112, 519–531.
Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W. G., Ross, J., Haug, J., Johnson, T., Feng, J. Q., Harris, S., Wiedemann, L. M., Mishina, Y., and Li, L. (2003) Identification of the haematopoietic stem cell niche and control of the niche size, Nature 425, 836–841.
Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C., and Morrison, S. J. (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells, Cell 121, 1109–1121.
Kiel, M. J., and Morrison, S. J. (2008) Uncertainty in the niches that maintain haematopoietic stem cells, Nat Rev Immunol 8, 290–301.
Ninomiya, M., Abe, A., Katsumi, A., Xu, J., Ito, M., Arai, F., Suda, T., Kiyoi, H., Kinoshita, T., and Naoe, T. (2007) Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice, Leukemia 21, 136–142.
Cristofanilli, M., Hayes, D. F., Budd, G. T., Ellis, M. J., Stopeck, A., Reuben, J. M., Doyle, G. V., Matera, J., Allard, W. J., Miller, M. C., Fritsche, H. A., Hortobagyi, G. N., and Terstappen, L. W. (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer, J Clin Oncol 23, 1420–1430.
Smerage, J. B., and Hayes, D. F. (2008) The prognostic implications of circulating tumor cells in patients with breast cancer, Cancer Invest 26, 109–114.
Braun, S., Pantel, K., Muller, P., Janni, W., Hepp, F., Kentenich, C. R., Gastroph, S., Wischnik, A., Dimpfl, T., Kindermann, G., Riethmuller, G., and Schlimok, G. (2000) Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer, N Engl J Med 342, 525–533.
Gebauer, G., Fehm, T., Merkle, E., Beck, E. P., Lang, N., and Jager, W. (2001) Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up, J Clin Oncol 19, 3669–3674.
Lin, E. H., Hassan, M., Li, Y., Zhao, H., Nooka, A., Sorenson, E., Xie, K., Champlin, R., Wu, X., and Li, D. (2007) Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence, Cancer 110, 534–542.
Mehra, N., Penning, M., Maas, J., Beerepoot, L. V., van Daal, N., van Gils, C. H., Giles, R. H., and Voest, E. E. (2006) Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases, Clin Cancer Res 12, 4859–4866.
Acknowledgements
Preparation of this chapter was financed by the Science Foundation Ireland Strategic Research Cluster, Molecular Therapeutics for Cancer, Ireland (08/SRC/B1410: L. O’D. and J.C.). The authors thank Dr. Bo Rueda and staff at the Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, USA, where this work was undertaken.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Friel, A.M., Crown, J., O’Driscoll, L. (2011). Analysis of Gene Expression as Relevant to Cancer Cells and Circulating Tumour Cells. In: O'Driscoll, L. (eds) Gene Expression Profiling. Methods in Molecular Biology, vol 784. Humana Press. https://doi.org/10.1007/978-1-61779-289-2_5
Download citation
DOI: https://doi.org/10.1007/978-1-61779-289-2_5
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-288-5
Online ISBN: 978-1-61779-289-2
eBook Packages: Springer Protocols