OSTP as a novel peptide specifically targeting human ovarian cancer

Yang,Chen; He,Xiaojuan; Liu,Xiaomin; Tang,Zheng; Liang,Xiaoqiu

doi:10.3892/or.2015.4066

OSTP as a novel peptide specifically targeting human ovarian cancer

Authors:
- Chen Yang
- Xiaojuan He
- Xiaomin Liu
- Zheng Tang
- Xiaoqiu Liang
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Affiliations: Cancer Research Institute, University of South China, Hengyang, Hunan 421001, P.R. China, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: June 15, 2015 https://doi.org/10.3892/or.2015.4066
Pages: 972-978

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Abstract

Ovarian cancer is a disease that seriously threatens the health of women and results in a high mortality rate. The present study aimed to investigate the novel peptide OSTP (peptide for specifically targeting ovarian cancer) to provide new methods for the effective diagnosis and treatment of ovarian cancer. The nude mouse ovarian cancer model was established. With the use of phage peptide display in vivo, a novel 7-amino peptide for specific binding to ovarian cancer was screened from the FliTrx bacterial peptide display system. OSTP was compounded and labeled with fluorescent pigment 5-FAM. The specificity and affinity of OSTP were tested in the ovarian cancer cell line A2780 in vitro. The tumor-targeting assays of OSTP were performed in vivo by injecting 5-FAM-OSTP into tumor-bearing mice. Clinical tissue specimens were tested by fluorescence staining following the addition of 5-FAM-OSTP. We found that the peptide specifically bound to ovarian cancer A2780 cells. Cell fluorescence staining showed that 5-FAM-OSTP obviously and specifically bound to ovarian cancer A2780 cells, particularly to the cell membrane. One hour after i.v. peptide injection, 5-FAM-OSTP specifically targeted the tumor tissues in the tumor-bearing mice. In the human pathological sections, 5-FAM-OSTP exhibited strong specific binding to ovarian cancer tissues. The cell membrane and cytoplasm of the cells exhibited a fluorescent signal. This signal was more evident on the cell membrane. The present results suggest that OSTP is a potential strategy for the development of new diagnostic strategies and drug-targeted therapies for ovarian cancer.

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1	Gondos A, Bray F, Hakulinen T and Brenner H: EUNICE Survival Working Group: Trends in cancer survival in 11 European populations from 1990 to 2009: A model-based analysis. Ann Oncol. 20:564–573. 2009. View Article : Google Scholar
2	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI
3	Yang NN, Yan YQ and Gong J: An analysis on incidence and mortality of ovarian cancer from 2003 to 2007 in China. China Cancer. 21:401–405. 2012.
4	Yang D, Sun Y, Hu L, Zheng H, JI P, Pecot CV, Zhao Y, Reynolds S, Cheng H, Rupaimoole R, et al: Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell. 23:186–199. 2013. View Article : Google Scholar : PubMed/NCBI
5	Coleman RL, Monk BJ, Sood AK and Herzog TJ: Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 10:211–224. 2013. View Article : Google Scholar : PubMed/NCBI
6	Zhu AX and Hezel AF: Development of molecularly targeted therapies in biliary tract cancers: Reassessing the challenges and opportunities. Hepatology. 53:695–704. 2011. View Article : Google Scholar : PubMed/NCBI
7	Masoumi Moghaddam S, Amini A, Morris DL and Pourgholami MH: Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer. Cancer Metastasis Rev. 31:143–162. 2012. View Article : Google Scholar :
8	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
9	Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA and Horowitz IR: Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: A phase ii trial of the Gynecologic Oncology Group. J Clin Oncol. 21:283–290. 2003. View Article : Google Scholar : PubMed/NCBI
10	Tebbutt N, Pedersen MW and Johns TG: Targeting the ERBB family in cancer: Couples therapy. Nat Rev Cancer. 13:663–673. 2013. View Article : Google Scholar : PubMed/NCBI
11	Morotti M, Valenzano Menada M, Venturini PL, Mammoliti S and Ferrero S: Pemetrexed disodium in ovarian cancer treatment. Expert Opin Investig Drugs. 21:437–449. 2012. View Article : Google Scholar : PubMed/NCBI
12	Oei AL, Sweep FC, Thomas CM, Boerman OC and Massuger LF: The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (Review). Int J Oncol. 32:1145–1157. 2008. View Article : Google Scholar : PubMed/NCBI
13	Leone Roberti Maggiore U, Bellati F, Ruscito I, Gasparri ML, Alessandri F, Venturini PL and Ferrero S: Monoclonal antibodies therapies for ovarian cancer. Expert Opin Biol Ther. 13:739–764. 2013. View Article : Google Scholar : PubMed/NCBI
14	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
15	Corso S, Ghiso E, Cepero V, Sierra JR, Migliore C, Bertotti A, Trusolino L, Comoglio PM and Giordano S: Activation of HER family members in gastric carcinoma cells mediates resistance to MET inhibition. Mol Cancer. 9:1212010. View Article : Google Scholar : PubMed/NCBI
16	Smith GP: Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science. 228:1315–1317. 1985. View Article : Google Scholar : PubMed/NCBI
17	Wang N, Thuraisingam T, Fallavollita L, Ding A, Radzioch D and Brodt P: The secretory leukocyte protease inhibitor is a type 1 insulin-like growth factor receptor-regulated protein that protects against liver metastasis by attenuating the host proinflammatory response. Cancer Res. 66:3062–3070. 2006. View Article : Google Scholar : PubMed/NCBI
18	Li M, Anastassiades CP, Joshi B, Komarck CM, Piraka C, Elmunzer BJ, Turgeon DK, Johnson TD, Appelman H, Beer DG, et al: Affinity peptide for targeted detection of dysplasia in Barrett’s esophagus. Gastroenterology. 139:1472–1480. 2010. View Article : Google Scholar : PubMed/NCBI
19	Yang W, Luo D, Wang S, Wang R, Chen R, Liu Y, Zhu T, Ma X, Liu R, Xu G, et al: TMTP1, a novel tumor-homing peptide specifically targeting metastasis. Clin Cancer Res. 14:5494–5502. 2008. View Article : Google Scholar : PubMed/NCBI
20	Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM, Hanahan D, Mattrey RF and Ruoslahti E: Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell. 16:510–520. 2009. View Article : Google Scholar : PubMed/NCBI
21	Noren KA and Noren CJ: Construction of high-complexity combinatorial phage display peptide libraries. Methods. 23:169–178. 2001. View Article : Google Scholar : PubMed/NCBI
22	Bamias A, Pignata S and Pujade-Lauraine E: Angiogenesis: A promising therapeutic target for ovarian cancer. Crit Rev Oncol Hematol. 84:314–326. 2012. View Article : Google Scholar : PubMed/NCBI
23	Vosjan MJ, Vercammen J, Kolkman JA, Stigter-van Walsum M, Revets H and van Dongen GA: Nanobodies targeting the hepatocyte growth factor: Potential new drugs for molecular cancer therapy. Mol Cancer Ther. 11:1017–1025. 2012. View Article : Google Scholar : PubMed/NCBI
24	Zwick MB, Shen J and Scott JK: Phage-displayed peptide libraries. Curr Opin Biotechnol. 9:427–436. 1998. View Article : Google Scholar : PubMed/NCBI
25	Ferrara N and Kerbel RS: Angiogenesis as a therapeutic target. Nature. 438:967–974. 2005. View Article : Google Scholar : PubMed/NCBI
26	Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G and Cheresh DA: Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 79:1157–1164. 1994. View Article : Google Scholar : PubMed/NCBI
27	Li XB, Schluesener HJ and Xu SQ: Molecular addresses of tumors: Selection by in vivo phage display. Arch Immunol Ther Exp (Warsz). 54:177–181. 2006. View Article : Google Scholar
28	Pasqualini R and Ruoslahti E: Organ targeting in vivo using phage display peptide libraries. Nature. 380:364–366. 1996. View Article : Google Scholar : PubMed/NCBI
29	Pasqualini R, Koivunen E and Ruoslahti E: Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol. 15:542–546. 1997. View Article : Google Scholar : PubMed/NCBI
30	Arap W, Pasqualini R and Ruoslahti E: Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 279:377–380. 1998. View Article : Google Scholar : PubMed/NCBI
31	Teesalu T, Sugahara KN, Kotamraju VR and Ruoslahti E: C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc natl Acad Sci USA. 106:16157–16162. 2009. View Article : Google Scholar : PubMed/NCBI
32	Xiao K, Li Y, Lee JS, Gonik AM, Dong T, Fung G, Sanchez E, Xing L, Cheng HR, Luo J, et al: ‘OA02’ peptide facilitates the precise targeting of paclitaxel-loaded micellar nanoparticles to ovarian cancer in vivo. Cancer Res. 72:2100–2110. 2012. View Article : Google Scholar : PubMed/NCBI
33	Li K, Lv XX, Hua F, Lin H, Sun W, Cao WB, Fu XM, Xie J, Yu JJ, Li Z, et al: Targeting acute myeloid leukemia with a proapoptotic peptide conjugated to a toll-like receptor 2-mediated cell-penetrating peptide. Int J Cancer. 134:692–702. 2014. View Article : Google Scholar