Identification of a Novel Peptide Ligand of Human Vascular Endothelia Growth Factor Receptor 3 for Targeted Tumour Diagnosis and Therapy

Xin, Qin; Wan, Yi; Li, Meng; Xue, Xiaochang; Wu, Shouzhen; Zhang, Cun; You, Yanjie; Jiang, Changli; Liu, Yan; Zhu, Wenhua; Ran, Yonggang; Zhang, Zhen; Han, Wei; Zhang, Yingqi

doi:10.1093/jb/mvm109

Cited by 17 publications

(15 citation statements)

References 18 publications

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“…Using ovarian carcinoma tissues, the co-localization of peptide III with VEGFR-3 in the endothelial cells of lymphatic vessels was confirmed. This result is consistent with another published VEGFR-3-targeted peptide that could specifically bind VEGFR-3-positive carcinoma cells [ 33 ]. These results suggest that peptide III may also be a potential carrier for ovarian cancer biotherapy, which will be analyzed in further in vivo studies.…”

Section: Discussionsupporting

confidence: 93%

Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Shi¹,

Wu²,

Li³

2015

J Gynecol Oncol

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ObjectiveVascular endothelial growth factor (VEGF) interaction with its receptor, VEGFR-3/Flt-4, regulates lymphangiogenesis. VEGFR-3/Flt-4 expression in cancer cells has been correlated with clinical stage, lymph node metastasis, and lymphatic invasion. The objective of this study is to identify a VEGFR-3/Flt-4-interacting peptide that could be used to inhibit VEGFR-3 for ovarian cancer therapy.MethodsThe extracellular fragment of recombinant human VEGFR-3/Flt-4 (rhVEGFR-3/Flt-4) fused with coat protein pIII was screened against a phage-displayed random peptide library. Using affinity enrichment and enzyme-linked immunosorbent assay (ELISA) screening, positive clones of phages were amplified. Three phage clones were selected after four rounds of biopanning, and the specific binding of the peptides to rhVEGFR-3 was detected by ELISA and compared with that of VEGF-D. Immunohistochemistry and immunofluorescence analyses of ovarian cancer tissue sections was undertaken to demonstrate the specificity of the peptides.ResultsAfter four rounds of biopanning, ELISA confirmed the specificity of the enriched bound phage clones for rhVEGFR-3. Sequencing and translation identified three different peptides. Non-competitive ELISA revealed that peptides I, II, and III had binding affinities for VEGFR-3 with Kaff (affinity constant) of 16.4±8.6 µg/mL (n=3), 9.2±2.1 µg/mL (n=3), and 174.8±31.1 µg/mL (n=3), respectively. In ovarian carcinoma tissue sections, peptide III (WHWLPNLRHYAS), which had the greatest binding affinity, also co-localized with VEGFR-3 in endothelial cells lining lymphatic vessels; its labeling of ovarian tumors in vivo was also confirmed.ConclusionThese finding showed that peptide III has high specificity and activity and, therefore, may represent a potential therapeutic approach to target VEGF-VEGFR-3 signaling for the treatment or diagnosis of ovarian cancer.

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Section: Discussionsupporting

confidence: 93%

Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Shi¹,

Wu²,

Li³

2015

J Gynecol Oncol

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“…Peptide P1, CSDSWHYWC, exhibited the highest affinity to VEGFR-3 in phage ELISA. Chemically synthesized P1 can bind to VEGFR-3 positive carcinoma cells with specificity [53]. …”

Section: Biological Library Methodsmentioning

confidence: 99%

Tumor-targeting peptides from combinatorial libraries

Liu

Xiao

et al. 2017

Advanced Drug Delivery Reviews

165

102

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Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors.

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“…The most common screening strategy involves purifying a specific target, absorbing it to an affinity resin or ELISA plate, and screening for binding by adding a phage peptide library [31], [32]. This method requires further confirmation of binding using the native form of the target in cells or tissues because peptides selected using purified recombinant protein might not be capable of accessing their targets in living cells.…”

Section: Discussionmentioning

confidence: 99%

Screening of a Specific Peptide Binding to VPAC1 Receptor from a Phage Display Peptide Library

Tang

Huang

et al. 2013

PLoS ONE

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Background/PurposeThe VPAC1 receptor, a member of the vasoactive intestinal peptide receptors (VIPRs), is overexpressed in the most frequently occurring malignant tumors and plays a major role in the progression and angiogenesis of a number of malignancies. Recently, phage display has become widely used for many applications, including ligand generation for targeted imaging, drug delivery and therapy. In this work, we developed a panning procedure using a phage display peptide library to select a peptide that specifically binds to the VPAC1 receptor to develop a novel targeted probe for molecular imaging and therapy.MethodsCHO-K1 cells stably expressing VPAC1 receptors (CHO-K1/VPAC1 cells) were used to select a VPAC1-binding peptide from a 12-mer phage peptide library. DNA sequencing and homologous analysis of the randomly selected phage clones were performed. A cellular ELISA was used to determine the most selectively binding peptide for further investigation. Binding specificity to the VPAC1 receptor was analyzed by competitive inhibition ELISA and flow cytometry. The binding ability of the selected peptide to CHO-K1/VPAC1 cells and colorectal cancer (CRC) cell lines was confirmed using fluorescence microscopy and flow cytometry.ResultsA significant enrichment of phages that specifically bound to CHO-K1/VPAC1 cells was obtained after four rounds of panning. Of the selected phage clones, 16 out of 60 shared the same peptide sequence, GFRFGALHEYNS, which we termed the VP2 peptide. VP2 and vasoactive intestinal peptide (VIP) competitively bound to the VPAC1 receptor. More importantly, we confirmed that VP2 specifically bound to CHO-K1/VPAC1 cells and several CRC cell lines.ConclusionOur results demonstrate that the VP2 peptide could specifically bind to VPAC1 receptor and several CRC cell lines. And VP2 peptide may be a potential candidate to be developed as a useful diagnostic molecular imaging probe for early detection of CRC.

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Identification of a Novel Peptide Ligand of Human Vascular Endothelia Growth Factor Receptor 3 for Targeted Tumour Diagnosis and Therapy

Cited by 17 publications

References 18 publications

Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Tumor-targeting peptides from combinatorial libraries

Screening of a Specific Peptide Binding to VPAC1 Receptor from a Phage Display Peptide Library

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