A potential peptide vector that allows targeted delivery of a desired fusion protein into the human breast cancer cell line MDA‑MB‑231

Liu,Wei Qing; Yang,Jun; Hong,Min; Gao,Chang E.; Dong,Jian

doi:10.3892/ol.2016.4538

A potential peptide vector that allows targeted delivery of a desired fusion protein into the human breast cancer cell line MDA‑MB‑231

Authors:
- Wei Qing Liu
- Jun Yang
- Min Hong
- Chang E. Gao
- Jian Dong
View Affiliations

Affiliations: Department of Internal Medicine Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: May 6, 2016 https://doi.org/10.3892/ol.2016.4538
Pages: 3943-3952
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Effective control of breast cancer has been primarily hampered by a lack of tumor specificity in treatments. One potential way to improve targeting specificity is to develop novel vectors that specifically bind to and are internalized by tumor cells. Through a phage display library, an 11‑L‑amino acid peptide, PI (sequence, CASPSGALRSC), was selected. PI was labeled with fluorescein isothiocyanate (FITC) and named PI‑FITC. Subsequently, the specific affinity of PI‑FITC to MDA‑MB‑231 human breast cancer cells and other cancer cell lines was observed by confocal microscopy. Our previous study established that PI‑FITC also shows affinity to Calu‑1 human lung carcinoma cells and major histocompatibility complex class I antigen molecules; therefore, the cytomembrane proteins of the cell lines were analyzed to determine those that were common to the two cell lines and may be associated with transmembrane transduction. To further test the delivery ability of PI to MDA‑MB‑231 cells, PI‑glutathione‑S‑transferase (GST) was constructed and the internalization of this fusion protein was visualized by immunofluorescence microscopy. The results revealed that PI exhibited specific affinity to MDA‑MB‑231 cells. Use of membrane transport inhibitors indicated that macropinocytosis and caveolin‑mediated endocytosis may be involved in the endocytosis of PI. In addition, 11 membrane proteins common to MDA‑MB‑231 and Calu‑1 may be associated with transmembrane transduction. In summary, PI was able to deliver PI‑GST into MDA‑MB‑231 cells. Thus, PI could be modified to be a potential vector, and may contribute to the development of targeted therapeutic strategies for breast cancer.

View Figures

View References

1	Cooke SP, Boxer GM, Lawrence L, Pedley RB, Spencer DI, Begent RH and Chester KA: A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor: Receptor complex. Cancer Res. 61:3653–3659. 2001.PubMed/NCBI
2	Miller CR, Buchsbaum DJ, Reynolds PN, Douglas JT, Gillespie GY, Mayo MS, Raben D and Curiel DT: Differential susceptibility of primary and established human glioma cells to adenovirus infection: Targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res. 58:5738–5748. 1998.PubMed/NCBI
3	Baselga J, Norton L, Albanell J, Kim YM and Mendelsohn J: Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2 overexpressing human breast cancer xenografts. Cancer Res. 58:2825–2831. 1998.PubMed/NCBI
4	Ruoslahti E and Pierschbacher MD: New perspectives in cell adhesion: RGD and integrins. Science. 238:491–497. 1987. View Article : Google Scholar : PubMed/NCBI
5	Frankel AD and Pabo CO: Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 55:1189–1193. 1988. View Article : Google Scholar : PubMed/NCBI
6	Green M and Loewenstein PM: Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans activator protein. Cell. 55:1179–1188. 1988. View Article : Google Scholar : PubMed/NCBI
7	Elliott G and O'Hare P: Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell. 88:223–233. 1997. View Article : Google Scholar : PubMed/NCBI
8	Muthumani K, Lambert VM, Shanmugam M, Thieu KP, Choo AY, Chung JC, Satishchandran A, Kim JJ, Weiner DB and Ugen KE: Anti-tumor activity mediated by protein and peptide transduction of HIV viral protein R (Vpr). Cancer Biol Ther. 8:180–187. 2009. View Article : Google Scholar : PubMed/NCBI
9	Liu CS, Kong B, Ma DX, Wang WX, Mq W and Kao E: VP22 enhanced intercellular trafficking of HSV thymidine kinase promoted an effective cell killing effect at lower concentration of ganciclovir. Chin J Cancer Biother. 8:93–97. 2001.
10	Albarran B, To R and Stayton PS: A TAT-streptavidin fusion protein directs uptake of biotinylated cargo into mammalian cells. Protein Eng Des Sel. 18:147–152. 2005. View Article : Google Scholar : PubMed/NCBI
11	Xiong F, Xiao S, Peng F, Zheng H, Yu M, Ruan Y, Li W, Shang Y, Zhao C, Zhou W, et al: Herpes simplex virus VP22 enhances adenovirus-mediated microdystrophin gene transfer to skeletal muscles in dystrophin-deficient (mdx) mice. Hum Gene Ther. 18:490–501. 2007. View Article : Google Scholar : PubMed/NCBI
12	Ivanenkov VV, Felici F and Menon AG: Targeted delivery of multivalent phage display vectors into mammalian cells. Biochim Biophys Acta. 1448:463–472. 1999. View Article : Google Scholar : PubMed/NCBI
13	Schwarze SR, Hruska KA and Dowdy SF: Protein transduction: Unrestricted delivery into all cells? Trends Cell Biol. 10:290–295. 2000. View Article : Google Scholar : PubMed/NCBI
14	Ho A, Schwarze SR, Mermelstein SJ, Waksman G and Dowdy SF: Synthetic protein transduction domains: Enhanced transduction potential in vitro and in vivo. Cancer Res. 61:474–477. 2001.PubMed/NCBI
15	Rajotte D and Ruoslahti E: Membrane dipetidase is the receptor for a lung-targeting peptide dentified by in vivo phage display. J Biol Chem. 274:11593–11598. 1999. View Article : Google Scholar : PubMed/NCBI
16	Dente L, Vetriani C, Zucconi A, Pelicci G, Lanfrancone L, Pelicci PG and Cesareni G: Modified phage peptide libraries as a tool to study specificity of phosphorylation and recognition of tyrosine containing peptide. J Mol Biol. 269:694–703. 1997. View Article : Google Scholar : PubMed/NCBI
17	Liu F, Guo XR, Gong HX, Ni YH, Fei L, Pan XQ, Guo M and Chen RH: A resistin binding peptide selected by phage display inhibits 3T3-L1 preadipocyte differentiation. Chin Med J (Engl). 119:496–503. 2006.PubMed/NCBI
18	Pires D, Bemquerer M and Nascimento C: Some mechanistic aspects on Fmoc solid phase peptide synthesis. Int J Pept Res Ther. 20:53–69. 2014. View Article : Google Scholar
19	West MA, Bretscher MS and Watts C: Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J Cell Biol. 109:2731–2739. 1989. View Article : Google Scholar : PubMed/NCBI
20	Furuchi T and Anderson RG: Cholesterol depletion of caveolae causes hyperactivation of extracellular signal-related kinase (ERK). J Biol Chem. 273:21099–21104. 1998. View Article : Google Scholar : PubMed/NCBI
21	Subtil A, Hémar A and Dautry-Varsat A: Rapid endocytosis of interleukin 2 receptors when clathrin-coated pit endocytosis is inhibited. J Cell Sci. 107:3461–3468. 1994.PubMed/NCBI
22	Garcia-Lora A, Algarra I and Garrido F: MHC class I antigens, immune surveillance and tumor immune escape. J Cell Physiol. 195:346–355. 2003. View Article : Google Scholar : PubMed/NCBI
23	Adessi C, Miege C, Albrieux C and Rabilloud T: Two-dimensional electrophoresis of membrane proteins: A current challenge for immobilized pH gradients. Electrophoresis. 18:127–135. 1997. View Article : Google Scholar : PubMed/NCBI
24	Huebener N, Lange B, Lemmel C, Rammensee HG, Strandsby A, Wenkel J, Jikai J, Zeng Y, Gaedicke G and Lode HN: Vaccination with minigenes encoding for novel ‘self’ antigens are effective in DNA-vaccination against neuroblastoma. Cancer Lett. 197:211–217. 2003. View Article : Google Scholar : PubMed/NCBI
25	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
26	Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 365:1687–1717. 2005. View Article : Google Scholar : PubMed/NCBI
27	Dean-Colomb W and Esteva FJ: Her2-positive breast cancer: Herceptin and beyond. Eur J Cancer. 44:2806–2812. 2008. View Article : Google Scholar : PubMed/NCBI
28	Davoli A, Hocevar BA and Brown TL: Progression and treatment of HER2-positive breast cancer. Cancer Chemother Pharmacol. 65:611–623. 2010. View Article : Google Scholar : PubMed/NCBI
29	Fogelman DR, Kopetz S and Eng C: Emerging drugs for colorectal cancer. Expert Opin Emerg Drugs. 13:629–642. 2008. View Article : Google Scholar : PubMed/NCBI
30	Kim R and Toge T: Changes in therapy for solid tumors: Potential for overcoming drug resistance in vivo with molecular targeting agents. Surg Today. 34:293–303. 2004. View Article : Google Scholar : PubMed/NCBI
31	Ran JT, Zhou YN, Tang CW, Lu JR, Wu J, Lu H and Yang GD: Celecoxib induces apoptosis and inhibites angiogenesis in gastric cancer. Zhonghua Zhong Liu Za Zhi. 30:448–451. 2008.(In Chinese). PubMed/NCBI
32	Ortega J, Vigil CE and Chodkiewicz C: Current progress in targeted therapy for colorectal cancer. Cancer Control. 17:7–15. 2010.PubMed/NCBI
33	Mailliez A, Baldini C, Van JT, Servent V, Mallet Y and Bonneterre J: Nasal septum perforation: A side effect of bevacizumab chemotherapy in breast cancer patients. Br J Cancer. 103:772–775. 2010. View Article : Google Scholar : PubMed/NCBI
34	Takeda A, Loveman E, Harris P, Hartwell D and Welch K: Time to full publication of studies of anti-cancer medicines for breast cancer and the potential for publication bias: A short systematic review. Health Technol Assess. 12:1–46. 2008. View Article : Google Scholar : PubMed/NCBI
35	Brown KC: Peptidic tumor targeting agents: The road from phage display peptide selections to clinical applications. Curr Pharm Des. 16:1040–1054. 2010. View Article : Google Scholar : PubMed/NCBI
36	Laakkonen P and Vuorinen K: Homing peptides as targeted delivery vehicles. Integr Biol (Camb). 2:326–337. 2010. View Article : Google Scholar : PubMed/NCBI
37	Miller WH, Alberts DP, Bhatnagar PK, Bondinell WE, Callahan JF, Calvo RR, Cousins RD, Erhard KF, Heerding DA, Keenan RM, et al: Discovery of orally active nonpeptide vitronectin receptor antagonists based on a 2-benzazepine gly-Asp mimetic. J Med Chem. 43:22–26. 2000. View Article : Google Scholar : PubMed/NCBI
38	Zhao H, Wang JC, Sun QS, Luo CL and Zhang Q: RGD-based strategies for improving antitumor activity of paclitaxel-loaded liposomes in nude mice xenografted with human ovarian cancer. J Drug Target. 17:10–18. 2009. View Article : Google Scholar : PubMed/NCBI
39	Dong J, Liu WQ, Jiang AM, Zhang KJ and Chen MQ: A novel peptide, selected from phage display library of random peptides, can efficiently target into human breast cancer cell. Chinese Science Bulletin. 53:860–867. 2008.
40	Zitzmann S, Krämer S, Mier W, Hebling U, Altmann A, Rother A, Berndorff D, Eisenhut M and Haberkorn U: Identification and evaluation of a new tumor cell-binding peptide, FROP-1. J Nucl Med. 48:965–972. 2007. View Article : Google Scholar : PubMed/NCBI