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A CD44 specific peptide developed by phage display for targeting gastric cancer

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Abstract

Objective

To develop a peptide probe that could be used for gastric cancer detection via binding to CD44 protein with specificity and affinity.

Results

A 12-mer phage peptide library was screened against immobilized CD44 protein. Bound phage counts using ELISA were performed to identify phage clones carrying the most highly selective peptide, which termed RP-1. Immunofluorescence and flow cytometry analysis indicated that the consensus peptide RP-1 could bind to CD44-positive gastric cancer cells with mean fluorescence intensities significantly higher than that of CD44-negative cells. CD44 knockdown led to decreased binding activity of RP-1 to the same cell line. Tissue array technique was used to identify the relationship (r = 0.556) between peptide binding and CD44 detection on gastric cancer tissues. Further, the hyaluronan-binding domain of CD44 was docked with RP-1 using computer modeling/docking approaches, revealing a RP-1/CD44 interaction with geometrical and energy match (−8.6 kcal/mol).

Conclusions

The RP-1 peptide we screened exhibits affinity and specificity to CD44 on cells and has the potential to be used as a candidate probe for gastric cancer cell targeting.

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References

  • Atreya R, Goetz M (2013) Molecular imaging in gastroenterology. Nat Rev Gastroenterol Hepatol 10:704–712

    Article  PubMed  Google Scholar 

  • Chen W, Zhang X, Chu C, Cheung WL, Ng L, Lam S, Chow A, Lau T, Chen M, Li Y et al (2013) Identification of CD44 + cancer stem cells in human gastric cancer. Hepatogastroenterology 60:949–954

    CAS  PubMed  Google Scholar 

  • Costantini TW, Eliceiri BP, Putnam JG, Bansal V, Baird A, Coimbra R (2012) Intravenous phage display identifies peptide sequences that target the burn-injured intestine. Peptides 38:94–99

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Goetz M, Wang TD (2010) Molecular imaging in gastrointestinal endoscopy. Gastroenterology 138(828–833):e821

    Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Miller SJ, Joshi BP, Feng Y, Gaustad A, Fearon ER, Wang TD (2011) In vivo fluorescence-based endoscopic detection of colon dysplasia in the mouse using a novel peptide probe. PLoS ONE 6:e17384

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Noren KA, Noren CJ (2001) Construction of high-complexity combinatorial phage display peptide libraries. Methods 23:169–178

    Article  CAS  PubMed  Google Scholar 

  • Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4:33–45

    Article  CAS  PubMed  Google Scholar 

  • Seaman ME, Contino G, Bardeesy N, Kelly KA (2010) Molecular imaging agents: impact on diagnosis and therapeutics in oncology. Expert Rev Mol Med 12:e20

    Article  PubMed Central  PubMed  Google Scholar 

  • Teriete P, Banerji S, Noble M, Blundell CD, Wright AJ, Pickford AR, Lowe E, Mahoney DJ, Tammi MI, Kahmann JD et al (2004) Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. Mol Cell 13:483–496

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Ong CW, Shi J, Srivastava S, Yan B, Cheng CL, Yong WP, Chan SL, Yeoh KG, Iacopetta B et al (2011) Sequential expression of putative stem cell markers in gastric carcinogenesis. Br J Cancer 105:658–665

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang H, Ma C, Li R, Guo Y, He Y, Wang X, Chen Y, Hou Y (2013) Selection and characterization of colorectal cancer cell-specific peptides. Biotechnol Lett 35:671–677

    Article  CAS  PubMed  Google Scholar 

  • Washington K, Gottfried MR, Telen MJ (1994) Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas. Hum Pathol 25:1043–1049

    Article  CAS  PubMed  Google Scholar 

  • Winder T, Ning Y, Yang D, Zhang W, Power DG, Bohanes P, Gerger A, Wilson PM, Lurje G, Tang LH et al (2011) Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma. Int J Cancer 129:1096–1104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xiao N, Cheng D, Wang Y, Chen L, Liu X, Dou S, Liu G, Liang M, Hnatowich DJ, Rusckowski M (2011) Identification of a high affinity TAG-72 binding peptide by phage display selection. Cancer Biol Ther 11:22–31

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, Wu Q, Gao L, Wu K, Nie Y et al (2012) Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem 113:302–312

    Article  CAS  PubMed  Google Scholar 

  • Yokozaki H (2000) Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int 50:767–777

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Xi H, Cai A, Xia Q, Wang XX, Lu C, Zhang Y, Song Z, Wang H, Li Q et al (2013) Not all side population cells contain cancer stem-like cells in human gastric cancer cell lines. Dig Dis Sci 58:132–139

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81172359 and 81472747).

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Correspondence to Shao-Ying Lu.

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The authors declare no conflict of interest.

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Zhang, D., Jia, H., Wang, Y. et al. A CD44 specific peptide developed by phage display for targeting gastric cancer. Biotechnol Lett 37, 2311–2320 (2015). https://doi.org/10.1007/s10529-015-1896-z

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  • DOI: https://doi.org/10.1007/s10529-015-1896-z

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