LymphedemaV1, Main, Exploration, bibRecord, 006140

Non-Peptide Small Molecule Regulators of Lymphangiogenesis

Identifieur interne : 006140 ( Main/Exploration ); précédent : 006139; suivant : 006141

Non-Peptide Small Molecule Regulators of Lymphangiogenesis

Auteurs : Changge Fang ; Marta Aparicio Miguel ; Ingalill Avis ; Alfredo Martinez ; Enrique Zudaire ; Frank Cuttitta

Source :

Lymphatic Research and Biology [ 1539-6851 ] ; 2009.

RBID : PMC:2843547

Abstract

Adrenomedullin (AM) and gastrin releasing peptide (GRP) are neuroendocrine peptides that have been previously implicated as regulators of angiogenesis and lymphangiogenesis. Using an immortalized human dermal microvascular lymphatic endothelial cell line stably transfected with red fluorescent protein (LEC/RFP), we demonstrate the ability of AM and GRP to augment tube formation complexity of this target cell in a dose-dependent manner. Maximum tube density was initiated at 1nM for both peptides, and as concentrations exceeded 10 nM a decrease in tube formation was noted, hence following a classic rise/fall biological response curve. In addition, we show that appropriate small molecule mimetics to neutralizing monoclonal antibodies of AM or GRP, at 1 μM concentration, can function to either inhibit (antagonist) or enhance (super agonist) peptide-induced tube formation of LEC/RFP. Our small molecule reagents by themselves have no activity, but in the presence of their respective peptides can mediate a positive or negative response, hence the super agonist designation. These compounds represent new regulatory drugs of the lymphatic system with possible patient application in the clinical management of edema and metastatic disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843547

DOI: 10.1089/lrb.2009.0033
PubMed: 20143917
PubMed Central: 2843547

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Adrenomedullin (AM) and gastrin releasing peptide (GRP) are neuroendocrine peptides that have been previously implicated as regulators of angiogenesis and lymphangiogenesis. Using an immortalized human dermal microvascular lymphatic endothelial cell line stably transfected with red fluorescent protein (LEC/RFP), we demonstrate the ability of AM and GRP to augment tube formation complexity of this target cell in a dose-dependent manner. Maximum tube density was initiated at 1n<italic>M</italic>
 for both peptides, and as concentrations exceeded 10 n<italic>M</italic>
 a decrease in tube formation was noted, hence following a classic rise/fall biological response curve. In addition, we show that appropriate small molecule mimetics to neutralizing monoclonal antibodies of AM or GRP, at 1 μ<italic>M</italic>
 concentration, can function to either inhibit (antagonist) or enhance (super agonist) peptide-induced tube formation of LEC/RFP. Our small molecule reagents by themselves have no activity, but in the presence of their respective peptides can mediate a positive or negative response, hence the super agonist designation. These compounds represent new regulatory drugs of the lymphatic system with possible patient application in the clinical management of edema and metastatic disease.</p>
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<name sortKey="Martinez, Alfredo" sort="Martinez, Alfredo" uniqKey="Martinez A" first="Alfredo" last="Martinez">Alfredo Martinez</name>
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<name sortKey="Zudaire, Enrique" sort="Zudaire, Enrique" uniqKey="Zudaire E" first="Enrique" last="Zudaire">Enrique Zudaire</name>
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Non-Peptide Small Molecule Regulators of Lymphangiogenesis

Non-Peptide Small Molecule Regulators of Lymphangiogenesis

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Abstract

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