Skip to main content
SpringerLink
Log in

Selection of Cancer Stem Cell–Targeting Agents Using Bacteriophage Display

  • Protocol
  • First Online:
Biomedical Engineering Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2394))

Abstract

There is a growing need to develop tumor targeting agents for aggressive cancers. Aggressive cancers frequently relapse and are resistant to various therapies. Cancer stem cells (CSCs) are believed to be the cause of relapse and the aggressive nature of many cancers. Targeting CSCs could lead to novel diagnostic and treatment options. Bacteriophage (phage) display is a powerful tool developed by George Smith in 1985 to aid in the discovery of CSC targeting agents. Phage display selections are typically performed in vitro against an immobilized target. There are inherent disadvantages with this technique that can be circumvented by performing phage display selections in vivo. However, in vivo phage display selections present new challenges. A combination of both in vitro and in vivo selections, however, can take advantage of both selection methods. In this chapter, we discuss in detail how to isolate a CSC like population of cells from an aggressive cancer cell line, perform in vivo and in vitro phage display selections against the CSCs, and then characterize the resulting phage/peptides for further use as a diagnostic and therapeutic tool.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Singh A, Settleman J (2010) EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29(34):4741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rich JN (2007) Cancer stem cells in radiation resistance. Cancer Res 67(19):8980–8984

    Article  CAS  PubMed  Google Scholar 

  3. Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol Off J Am Soc Clin Oncol 26(17):2839

    Article  CAS  Google Scholar 

  4. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275

    Article  CAS  PubMed  Google Scholar 

  5. Merlos-Suárez A et al (2011) The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell 8(5):511–524

    Article  CAS  PubMed  Google Scholar 

  6. Yu Y, Ramena G, Elble RC (2012) The role of cancer stem cells in relapse of solid tumors. Front Biosci (Elite Ed) 4(4):1528–1541

    Article  Google Scholar 

  7. Salnikov AV et al (2010) CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients. Int J Cancer 126(4):950–958

    CAS  PubMed  Google Scholar 

  8. Nguyen PH et al (2017) Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Clin Cancer Res 23(6):1586–1597

    Article  CAS  PubMed  Google Scholar 

  9. Lv L et al (2016) Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells. Tumour Biol 37(7):8811–8824

    Article  CAS  PubMed  Google Scholar 

  10. Todaro M et al (2014) CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell 14(3):342–356

    Article  CAS  PubMed  Google Scholar 

  11. Collins AT et al (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951

    Article  CAS  PubMed  Google Scholar 

  12. Hurt EM et al (2008) CD44+ CD24(−) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 98(4):756–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zoller M (2011) CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer 11(4):254–267

    Article  CAS  PubMed  Google Scholar 

  14. Peng Y, Prater AR, Deutscher SL (2017) Targeting aggressive prostate cancer-associated CD44v6 using phage display selected peptides. Oncotarget 8(49):86747

    Article  PubMed  PubMed Central  Google Scholar 

  15. Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228(4705):1315–1317

    Article  CAS  PubMed  Google Scholar 

  16. Smith GP, Petrenko VA (1997) Phage display. Chem Rev 97(2):391–410

    Article  CAS  PubMed  Google Scholar 

  17. Clackson T et al (1991) Making antibody fragments using phage display libraries. Nature 352(6336):624

    Article  CAS  PubMed  Google Scholar 

  18. Ahangarzadeh S et al (2019) Bicyclic peptides: types, synthesis and applications. Drug Discov Today 24(6):1311–1319

    Article  CAS  PubMed  Google Scholar 

  19. Omidfar K et al (2004) Production and characterization of a new antibody specific for the mutant EGF receptor, EGFRvIII, in Camelus bactrianus. Tumor Biol 25(4):179–187

    Article  CAS  Google Scholar 

  20. Goodchild SA et al (2011) Isolation and characterisation of ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries. Mol Immunol 48(15–16):2027–2037

    Article  CAS  PubMed  Google Scholar 

  21. Newton J, Deutscher SL (2008) Phage peptide display. In: Molecular imaging II. Springer, pp 145–163

    Chapter  Google Scholar 

  22. Newton JR et al (2006) In vivo selection of phage for the optical imaging of PC-3 human prostate carcinoma in mice. Neoplasia 8(9):772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Newton JR, Deutscher SL (2009) In vivo bacteriophage display for the discovery of novel peptide-based tumor-targeting agents. Methods Mol Biol 504:275–290

    Article  CAS  PubMed  Google Scholar 

  24. Kanki S et al (2011) Identification of targeting peptides for ischemic myocardium by in vivo phage display. J Mol Cell Cardiol 50(5):841–848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nicol CG et al (2009) Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature. FEBS Lett 583(12):2100–2107

    Article  CAS  PubMed  Google Scholar 

  26. Kelly KA et al (2006) In vivo phage display selection yields atherosclerotic plaque targeted peptides for imaging. Mol Imaging Biol 8(4):201

    Article  PubMed  Google Scholar 

  27. Zahid M et al (2010) Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice. PLoS One 5(8):e12252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Denby L et al (2007) Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Mol Ther 15(9):1647–1654

    Article  CAS  PubMed  Google Scholar 

  29. Tang B et al (2015) A flexible reporter system for direct observation and isolation of cancer stem cells. Stem Cell Reports 4(1):155–169

    Article  PubMed  Google Scholar 

  30. Jerabek-Willemsen M et al (2014) MicroScale thermophoresis: interaction analysis and beyond. J Mol Struct 1077:101–113

    Article  CAS  Google Scholar 

  31. Duhr S, Braun D (2006) Why molecules move along a temperature gradient. Proc Natl Acad Sci 103(52):19678–19682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Deutscher SL, Figueroa SD, Kumar SR (2009) Tumor targeting and SPECT imaging properties of an 111In-labeled galectin-3 binding peptide in prostate carcinoma. Nucl Med Biol 36(2):137–146

    Article  CAS  PubMed  Google Scholar 

  33. Kumar SR, Deutscher SL (2008) 111In-labeled galectin-3–targeting peptide as a SPECT agent for imaging breast tumors. J Nucl Med 49(5):796–803

    Article  CAS  PubMed  Google Scholar 

  34. Kumar SR et al (2010) In vitro and in vivo evaluation of 64Cu-radiolabeled KCCYSL peptides for targeting epidermal growth factor receptor-2 in breast carcinomas. Cancer Biother Radiopharm 25(6):693–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kumar SR, Quinn TP, Deutscher SL (2007) Evaluation of an 111In-radiolabeled peptide as a targeting and imaging agent for ErbB-2 receptor–expressing breast carcinomas. Clin Cancer Res 13(20):6070–6079

    Article  CAS  PubMed  Google Scholar 

  36. Srinivas PR et al (2002) Proteomics for cancer biomarker discovery. Clin Chem 48(8):1160–1169

    CAS  PubMed  Google Scholar 

  37. Schiess R, Wollscheid B, Aebersold R (2009) Targeted proteomic strategy for clinical biomarker discovery. Mol Oncol 3(1):33–44

    Article  CAS  PubMed  Google Scholar 

  38. Maebert K et al (2014) Cancer biomarker discovery: current status and future perspectives. Int J Radiat Biol 90(8):659–677

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Harry S. Truman Veterans Memorial Hospital and Department of Biochemistry, University of Missouri, Columbia, MO, USA

    Austin R. Prater & Susan L. Deutscher

Authors
  1. Austin R. Prater
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan L. Deutscher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Austin R. Prater .

Editor information

Editors and Affiliations

  1. Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA

    Avraham Rasooly

  2. Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA

    Houston Baker

  3. Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA

    Miguel R. Ossandon

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Prater, A.R., Deutscher, S.L. (2022). Selection of Cancer Stem Cell–Targeting Agents Using Bacteriophage Display. In: Rasooly, A., Baker, H., Ossandon, M.R. (eds) Biomedical Engineering Technologies. Methods in Molecular Biology, vol 2394. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1811-0_41

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1811-0_41

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1810-3

  • Online ISBN: 978-1-0716-1811-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation