The minimum element of a synthetic peptide required to block prostate tumor cell migration

Sroka, Thomas; Mařı́k, Jan; Pennington, Michael E.; Lam, Kit S.; Cress, Anne E.

doi:10.4161/cbt.5.11.3461

Cited by 13 publications

(12 citation statements)

References 43 publications

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“…Existing research concerning the treatment of HCC by the integrin α V subunit focuses on immunotherapy and gene therapy; these methods have partially entered the stage of clinical drug trials [ 21 ]. As previously reported, LM609 [ 22 , 23 ] and Vitaxin [ 24 , 25 ], the monoclonal antibodies of integrin α V β3, both inhibited the invasion of tumors in vivo . In gene therapy, tumor-specific ASODN or nuclear enzymes are primarily used to reduce or alter the expression configuration of the integrin α V subunit and interfere with α V -subunit-mediated adhesion, movement, and transfer.…”

Section: Discussionsupporting

confidence: 60%

Inhibitory Effects of PEI-RGD/125I-(αv) ASODN on Growth and Invasion of HepG2 Cells

Cai

Sun

et al. 2015

Med Sci Monit

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BackgroundTo investigate the in vitro inhibitory effects of PEI-RGD/125I-(αV)ASODN (PEI, polyethylenimine; RGD, Arg-Gly-Asp; ASODN, antisense oligodeoxynucleotide) on the growth and invasion of HepG2 cells.Material/MethodsASODN of the integrin αV-subunit was marked with 125I and underwent complexation with PEI-RGD, a PEI derivative. Next, PEI-RGD/125I-(αV) ASODN was introduced into HepG2 cells via receptor-mediated transfection, and its inhibition rate on HepG2 cell growth was tested using the methyl thiazolyl tetrazolium (MTT) method. The effects of PEI-RGD/125I-(αV) ASODN on HepG2 cell invasion ability were evaluated using the Boyden chamber assay.Results1) The 125I marking rate of (αV) ASODN was 73.78±4.09%, and the radiochemical purity was 96.68±1.38% (greater than 90% even after a 48-h incubation period at 37°C), indicating high stability. 2) The cytotoxicity assays showed that the cell inhibition rates did not differ significantly between the PEI-RGD/125I-(αV)ASODN group and the PEI-RGD/(αV) ASODN group, but they were both significantly higher than in the other groups and were positively correlated (r=0.879) with the dosage within a certain range. 3) The invasion assays showed that the inhibition rate was significantly greater in the PEI-RGD/125I-(αV) ASODN group compared to the other groups.ConclusionsPEI-RGD/125I-(αV) ASODN can efficiently inhibit the growth and proliferation of HepG2 cells and can also weaken their invasive ability.

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Section: Discussionsupporting

confidence: 60%

Inhibitory Effects of PEI-RGD/125I-(αv) ASODN on Growth and Invasion of HepG2 Cells

Cai

Sun

et al. 2015

Med Sci Monit

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“…To test the requirement for exosomal ITGβ 4 binding to laminin for lung tropism, we blocked integrin binding using RGD and HYD-1 peptides. Pre-incubation of 4175-LuT exosomes with HYD-1, which blocks laminin receptors 26 , markedly reduced exosome uptake in the lung, whereas RGD, which blocks fibronectin receptors but not ITGβ 4 (ref. 27 ), did not significantly alter exosome uptake in the lung ( Fig.…”

Section: Exosomal Tropism Requires Itgβ 4 and Itgβmentioning

confidence: 99%

Tumour exosome integrins determine organotropic metastasis

Hoshino

Costa-Silva

Shen

et al. 2015

Nature

4,026

3,929

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Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

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“…The aim of the present study was to identify the amino acid residues of importance for the binding of PEPHC1 to EGFRvIII. This was done by systematically replacing each amino acid residue with alanine (18). The alanine residues, Ala 11 and Ala 15 , were replaced by leucine.…”

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confidence: 99%

Identification of Amino Acid Residues in PEPHC1 Important for Binding to the Tumor‐Specific Receptor EGFRvIII

Hansen¹,

Pb²,

Pedersen³

et al. 2008

Chem Biol Drug Des

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EGFRvIII is a cancer-specific epidermal growth factor tyrosine kinase receptor mutation, expressed in different kinds of cancer, in particular ovarian, glioblastomas, and breast cancer. A peptide, PEPHC1, has previously been shown to bind selectively to EGFRvIII. An alanine scan was performed to identify the amino acid residues important for binding of PEPHC1 to EGFRvIII. The results indicate that the amino acid residues at the N-terminus of PEPHC1 are essential for the binding to the mutated receptor. One analog, [Ala(12)]PEPHC1, showed higher selective binding to EGFRvIII than PEPHC1. On the basis of these results, six truncated peptide analogs derived from the N-terminus of PEPHC1, H-HFIIL-NH2, H-HFIILG-NH2, H-HFIILGF-NH2, H-HFIILGFM-NH2, H-HFLIIGFMR-NH2, and H-HFLIIGFMRR-NH2 were synthesized and tested in the same manner. We observed that H-HFIIL-NH2 and H-HFIILG-NH2 showed almost threefold lower binding to the mutated receptor than PEPHC1, whereas the remainder showed 25% lower binding. The secondary structure of the PEPHC1 analogs was investigated by far UV circular dichroism spectroscopy and their binding correlated with various structural parameters such as charge, mean hydrophobicity (), and mean hydrophobic moment (). This work provides data, which will be useful in the development of novel peptide-based ligands for EGFRvIII-targeted diagnostics and therapy. This work was in part presented at the 17th International Symposium on Radiopharmaceutical Sciences, April 2007, Aachen, Germany.

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The minimum element of a synthetic peptide required to block prostate tumor cell migration

Cited by 13 publications

References 43 publications

Inhibitory Effects of PEI-RGD/125I-(αv) ASODN on Growth and Invasion of HepG2 Cells

Inhibitory Effects of PEI-RGD/125I-(αv) ASODN on Growth and Invasion of HepG2 Cells

Tumour exosome integrins determine organotropic metastasis

Identification of Amino Acid Residues in PEPHC1 Important for Binding to the Tumor‐Specific Receptor EGFRvIII

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