Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.
The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142412&type=printable |
| _version_ | 1826584226510667776 |
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| author | Birgit Piater Achim Doerner Ralf Guenther Harald Kolmar Bjoern Hock |
| author_facet | Birgit Piater Achim Doerner Ralf Guenther Harald Kolmar Bjoern Hock |
| author_sort | Birgit Piater |
| collection | DOAJ |
| description | The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF). Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX). CLN64 and a previously described single-stranded DNA (ssDNA) aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding. |
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| format | Article |
| id | doaj.art-199bedfe4e1d431d96598b6378713080 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T15:34:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-199bedfe4e1d431d96598b63787130802025-02-25T05:33:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014241210.1371/journal.pone.0142412Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.Birgit PiaterAchim DoernerRalf GuentherHarald KolmarBjoern HockThe human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF). Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX). CLN64 and a previously described single-stranded DNA (ssDNA) aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142412&type=printable |
| spellingShingle | Birgit Piater Achim Doerner Ralf Guenther Harald Kolmar Bjoern Hock Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. PLoS ONE |
| title | Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. |
| title_full | Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. |
| title_fullStr | Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. |
| title_full_unstemmed | Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. |
| title_short | Aptamers Binding to c-Met Inhibiting Tumor Cell Migration. |
| title_sort | aptamers binding to c met inhibiting tumor cell migration |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142412&type=printable |
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