Eintrag weiter verarbeiten
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis
Gespeichert in:
| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | Molecular Cancer Therapeutics, 8, 2009, 9, S. 2708-2717 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo |
|---|---|
| author |
Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo |
| spellingShingle |
Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo Molecular Cancer Therapeutics Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis Cancer Research Oncology |
| author_sort |
carriero, maria vincenza |
| spelling |
Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-09-0174 <jats:title>Abstract</jats:title><jats:p>The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe–dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an αv integrin–dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/αv association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein–expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. [Mol Cancer Ther 2009;8(9):2708–17]</jats:p> Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis Molecular Cancer Therapeutics |
| doi_str_mv |
10.1158/1535-7163.mct-09-0174 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA5LTAxNzQ |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA5LTAxNzQ |
| institution |
DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 |
| imprint |
American Association for Cancer Research (AACR), 2009 |
| imprint_str_mv |
American Association for Cancer Research (AACR), 2009 |
| issn |
1535-7163 1538-8514 |
| issn_str_mv |
1535-7163 1538-8514 |
| language |
English |
| mega_collection |
American Association for Cancer Research (AACR) (CrossRef) |
| match_str |
carriero2009structurebaseddesignofanurokinasetypeplasminogenactivatorreceptorderivedpeptideinhibitingcellmigrationandlungmetastasis |
| publishDateSort |
2009 |
| publisher |
American Association for Cancer Research (AACR) |
| recordtype |
ai |
| record_format |
ai |
| series |
Molecular Cancer Therapeutics |
| source_id |
49 |
| title |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_unstemmed |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_full |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_fullStr |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_full_unstemmed |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_short |
Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_sort |
structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-09-0174 |
| publishDate |
2009 |
| physical |
2708-2717 |
| description |
<jats:title>Abstract</jats:title><jats:p>The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe–dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an αv integrin–dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/αv association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein–expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. [Mol Cancer Ther 2009;8(9):2708–17]</jats:p> |
| container_issue |
9 |
| container_start_page |
2708 |
| container_title |
Molecular Cancer Therapeutics |
| container_volume |
8 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792347431148453897 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T17:55:10.908Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Structure-based+design+of+an+urokinase-type+plasminogen+activator+receptor%E2%80%93derived+peptide+inhibiting+cell+migration+and+lung+metastasis&rft.date=2009-09-01&genre=article&issn=1538-8514&volume=8&issue=9&spage=2708&epage=2717&pages=2708-2717&jtitle=Molecular+Cancer+Therapeutics&atitle=Structure-based+design+of+an+urokinase-type+plasminogen+activator+receptor%E2%80%93derived+peptide+inhibiting+cell+migration+and+lung+metastasis&aulast=Pavone&aufirst=Vincenzo&rft_id=info%3Adoi%2F10.1158%2F1535-7163.mct-09-0174&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792347431148453897 |
| author | Carriero, Maria Vincenza, Longanesi-Cattani, Immacolata, Bifulco, Katia, Maglio, Ornella, Lista, Liliana, Barbieri, Antonio, Votta, Giuseppina, Masucci, Maria Teresa, Arra, Claudio, Franco, Renato, De Rosa, Mario, Stoppelli, Maria Patrizia, Pavone, Vincenzo |
| author_facet | Carriero, Maria Vincenza, Longanesi-Cattani, Immacolata, Bifulco, Katia, Maglio, Ornella, Lista, Liliana, Barbieri, Antonio, Votta, Giuseppina, Masucci, Maria Teresa, Arra, Claudio, Franco, Renato, De Rosa, Mario, Stoppelli, Maria Patrizia, Pavone, Vincenzo, Carriero, Maria Vincenza, Longanesi-Cattani, Immacolata, Bifulco, Katia, Maglio, Ornella, Lista, Liliana, Barbieri, Antonio, Votta, Giuseppina, Masucci, Maria Teresa, Arra, Claudio, Franco, Renato, De Rosa, Mario, Stoppelli, Maria Patrizia, Pavone, Vincenzo |
| author_sort | carriero, maria vincenza |
| container_issue | 9 |
| container_start_page | 2708 |
| container_title | Molecular Cancer Therapeutics |
| container_volume | 8 |
| description | <jats:title>Abstract</jats:title><jats:p>The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe–dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an αv integrin–dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/αv association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein–expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. [Mol Cancer Ther 2009;8(9):2708–17]</jats:p> |
| doi_str_mv | 10.1158/1535-7163.mct-09-0174 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA5LTAxNzQ |
| imprint | American Association for Cancer Research (AACR), 2009 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2009 |
| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
| issn | 1535-7163, 1538-8514 |
| issn_str_mv | 1535-7163, 1538-8514 |
| language | English |
| last_indexed | 2024-03-01T17:55:10.908Z |
| match_str | carriero2009structurebaseddesignofanurokinasetypeplasminogenactivatorreceptorderivedpeptideinhibitingcellmigrationandlungmetastasis |
| mega_collection | American Association for Cancer Research (AACR) (CrossRef) |
| physical | 2708-2717 |
| publishDate | 2009 |
| publishDateSort | 2009 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | ai |
| recordtype | ai |
| series | Molecular Cancer Therapeutics |
| source_id | 49 |
| spelling | Carriero, Maria Vincenza Longanesi-Cattani, Immacolata Bifulco, Katia Maglio, Ornella Lista, Liliana Barbieri, Antonio Votta, Giuseppina Masucci, Maria Teresa Arra, Claudio Franco, Renato De Rosa, Mario Stoppelli, Maria Patrizia Pavone, Vincenzo 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-09-0174 <jats:title>Abstract</jats:title><jats:p>The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe–dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an αv integrin–dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/αv association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein–expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. [Mol Cancer Ther 2009;8(9):2708–17]</jats:p> Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis Molecular Cancer Therapeutics |
| spellingShingle | Carriero, Maria Vincenza, Longanesi-Cattani, Immacolata, Bifulco, Katia, Maglio, Ornella, Lista, Liliana, Barbieri, Antonio, Votta, Giuseppina, Masucci, Maria Teresa, Arra, Claudio, Franco, Renato, De Rosa, Mario, Stoppelli, Maria Patrizia, Pavone, Vincenzo, Molecular Cancer Therapeutics, Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis, Cancer Research, Oncology |
| title | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_full | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_fullStr | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_full_unstemmed | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_short | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_sort | structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| title_unstemmed | Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-09-0174 |