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Clinical and Translational Oncology

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01-06-2013 | Research Article

A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo phage display

Authors: A. Koivistoinen, I. I. K. Ilonen, K. Punakivi, J. V. Räsänen, H. Helin, E. I. Sihvo, M. Bergman, J. A. Salo

Published in: Clinical and Translational Oncology | Issue 6/2013

Abstract

Aim

To identify linear peptide homing to non-small cell lung cancer (NSCLC) tumor cells using ex vivo phage display method.

Materials and methods

Twenty-six clinical patient samples were used to identify linear homing peptide, which was exposed to NSCLC cell cultures and control cell lines to determine cell binding affinity and cell localization. Also, ex vivo biodistribution was analyzed using tumor-bearing mice.

Results

The panning yielded peptide enrichment with a core motif ^A/_SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected for characterization and named Thx-peptide. The in vitro binding properties of Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed that Thx-Alexa and fluorescein conjugates were located in a subset of perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma xenografts in mice.

Conclusion

Thx shows promise for targeted imaging and drug delivery.

Sun S, Schiller JH, Spinola M, Minna JD (2007) New molecularly targeted therapies for lung cancer. J Clin Invest 117:2740–2750CrossRefPubMed

Jain RK (1996) 1995 Whitaker lecture: delivery of molecules, particles, and cells to solid tumors. Ann Biomed Eng 24:457–473CrossRefPubMed

Heldin CH, Rubin K, Pietras K, Ostman A (2004) High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer 4:806–813CrossRefPubMed

Adessi C, Soto C (2002) Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem 9:963–978CrossRefPubMed

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

Nilsson F, Tarli L, Viti F, Neri D (2000) The use of phage display for the development of tumour targeting agents. Adv Drug Deliv Rev 43:165–196CrossRefPubMed

Laakkonen P, Akerman ME, Biliran H et al (2004) Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells. Proc Natl Acad Sci USA 101:9381–9386CrossRefPubMed

Shukla GS, Krag DN (2005) Selection of tumor-targeting agents on freshly excised human breast tumors using a phage display library. Oncol Rep 13:757–764PubMed

Zhang B, Zhang Y, Wang J et al (2007) Screening and identification of a targeting peptide to hepatocarcinoma from a phage display peptide library. Mol Med 13:246–254PubMed

10.

Newton JR, Kelly KA, Mahmood U, Weissleder R, Deutscher SL (2006) In vivo selection of phage for the optical imaging of PC-3 human prostate carcinoma in mice. Neoplasia 8:772–780CrossRefPubMed

11.

Yang W, Luo D, Wang S et al (2008) TMTP1, a novel tumor-homing peptide specifically targeting metastasis. Clin Cancer Res 14:5494–5502CrossRefPubMed

12.

Lee TY, Lin CT, Kuo SY, Chang DK, Wu HC (2007) Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery. Cancer Res 67:10958–10965CrossRefPubMed

13.

Zang L, Shi L, Guo J et al (2009) Screening and identification of a peptide specifically targeted to NCI-H1299 from a phage display peptide library. Cancer Lett 281:64–70CrossRefPubMed

14.

Oyama T, Sykes KF, Samli KN, Minna JD, Johnston SA, Brown KC (2003) Isolation of lung tumor specific peptides from a random peptide library: generation of diagnostic and cell-targeting reagents. Cancer Lett 202:219–230CrossRefPubMed

15.

Willats W (2002) Phage display: practicalities and prospects. Plant Mol Biol 50:837–854CrossRefPubMed

16.

Barbas CF III, Burton DR, Scott JK, Silverman GJ (2001) Phage display: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor New York, New York

17.

Boumrah D, Campbell MM, Fenner S, Kinsman RG (1997) Spacer molecules in peptide sequences: incorporation into analogues of atrial natriuretic factor. Tetrahedron 53:6977–6992CrossRef

18.

Joyce JA, Laakkonen P, Bernasconi M, Bergers G, Ruoslahti E, Hanahan D (2003) Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis. Cancer Cell 4:393–403CrossRefPubMed

19.

Hui X, Han Y, Liang S et al (2008) Specific targeting of the vasculature of gastric cancer by a new tumor-homing peptide CGNSNPKSC. J Control Release 131:86–93CrossRefPubMed

20.

Krag DN, Shukla GS, Shen GP et al (2006) Selection of tumor-binding ligands in cancer patients with phage display libraries. Cancer Res 66:7724–7733CrossRefPubMed

21.

Arap W, Kolonin MG, Trepel M et al (2002) Steps toward mapping the human vasculature by phage display. Nat Med 8:121–127CrossRefPubMed

22.

Maruta F, Akita N, Nakayama J et al (2007) Bacteriophage biopanning in human tumour biopsies to identify cancer-specific targeting ligands. J Drug Target 15:311–319CrossRefPubMed

23.

Kubo N, Akita N, Shimizu A, Kitahara H, Parker AL, Miyagawa S (2008) Identification of oligopeptide binding to colon cancer cells separated from patients using laser capture microdissection. J Drug Target 16:396–404CrossRefPubMed

24.

Lu H, Jin D, Kapila YL (2004) Application of laser capture microdissection to phage display peptide library screening. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98:692–697CrossRefPubMed

25.

Hong FD, Clayman GL (2000) Isolation of a peptide for targeted drug delivery into human head and neck solid tumors. Cancer Res 60:6551–6556PubMed

26.

Langel U (2006) Handbook of Cell-Penetrating Peptides, 2nd edn. Taylor & Francis Group, CRC PressCrossRef

27.

Futamura M, Nishimori H, Shiratsuchi T, Saji S, Nakamura Y, Tokino T (1999) Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1. J Hum Genet 44:52–56CrossRefPubMed

28.

Sasaki H, Moriyama S, Nakashima Y et al (2002) Expression of the MTA1 mRNA in advanced lung cancer. Lung Cancer 35:149–154CrossRefPubMed

29.

Holt JT, Thompson ME, Szabo C et al (1996) Growth retardation and tumour inhibition by BRCA1. Nat Genet 12:298–302CrossRefPubMed

30.

Wang Q, Zhang H, Kajino K, Greene MI (1998) BRCA1 binds c-myc and inhibits its transcriptional and transforming activity in cells. Oncogene 17:1939–1948CrossRefPubMed

Title: A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo phage display
Authors: A. Koivistoinen
I. I. K. Ilonen
K. Punakivi
J. V. Räsänen
H. Helin
E. I. Sihvo
M. Bergman
J. A. Salo
Publication date: 01-06-2013
Publisher: Springer Milan
Published in: Clinical and Translational Oncology / Issue 6/2013
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-012-0959-z

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Abstract

Aim

Materials and methods

Results

Conclusion

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