Abstract
Cancer stem-like cells (CSC) have been implicated in resistance to conventional chemotherapy as well as invasion and metastasis resulting in tumor relapse in majority of epithelial cancers including colorectal cancer. Hence, targeting CSC by small molecules is likely to improve therapeutic outcomes. Glycosaminoglycans (GAGs) are long linear polysaccharide molecules with varying degrees of sulfation that allows specific GAG-protein interaction which plays a key role in regulating cancer hallmarks such as cellular growth, angiogenesis, and immune modulation. However, identifying selective CSC-targeting GAG mimetic has been marred by difficulties associated with isolating and enriching CSC in vitro. Herein, we discuss two distinct methods, spheroid growth and EMT-transformed cells, to enrich CSC and set up medium- and high-throughput screen to identify selective CSC-targeting agents.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30
Donnenberg VS, Donnenberg AD (2005) Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol 45(8):872–877
Clarke MF et al (2006) Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344
Ricci-Vitiani L et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115
Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434(7035):843–850
Zhao C et al (2009) Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 458(7239):776–779
Reya T et al (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111
Piccirillo SG et al (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444(7120):761–765
Mishra L, Derynck R, Mishra B (2005) Transforming growth factor-beta signaling in stem cells and cancer. Science 310(5745):68–71
Esko JD, Kimata K, Lindahl U (2009) Proteoglycans and sulfated glycosaminoglycans. In: Varki A et al (eds) Essentials of glycobiology. Cold Spring Harbor Laboratory Press, NY
Tumova S, Woods A, Couchman JR (2000) Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions. Int J Biochem Cell Biol 32(3):269–288
Yip GW, Smollich M, Gotte M (2006) Therapeutic value of glycosaminoglycans in cancer. Mol Cancer Ther 5(9):2139–2148
Kim SH, Turnbull J, Guimond S (2011) Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 209(2):139–151
Gupta PB et al (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659
Yi SY et al (2013) Cancer stem cells niche: a target for novel cancer therapeutics. Cancer Treat Rev 39(3):290–296
Korkaya H, Wicha MS (2007) Selective targeting of cancer stem cells: a new concept in cancer therapeutics. BioDrugs 21(5):299–310
Kanwar SS et al (2010) The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer 9:212
Dontu G et al (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253–1270
Kanwar SS et al (2011) Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharm Res 28(4):827–838
Yu Y et al (2009) Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX. Transl Oncol 2(4):321–328
Kong D et al (2011) Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: are they cousins or twins? Cancers (Basel) 3(1):716–729
Mani SA et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715
Xia H et al (2010) miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and beta-catenin signaling. J Biol Chem 285(47):36995–37004
Acknowledgements
This work was supported by VA Merit Award to B.B.P.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Patel, N., Baranwal, S., Patel, B.B. (2015). A Strategic Approach to Identification of Selective Inhibitors of Cancer Stem Cells. In: Balagurunathan, K., Nakato, H., Desai, U. (eds) Glycosaminoglycans. Methods in Molecular Biology, vol 1229. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1714-3_41
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1714-3_41
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-1713-6
Online ISBN: 978-1-4939-1714-3
eBook Packages: Springer Protocols