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Biological Relevance of RGD-Integrin Subtype-Specific Ligands in Cancer |
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| Authors: | Saidu Sani Mélissa Messe Quentin Fuchs Marina Pierrevelcin Prof Patrice Laquerriere Prof Natacha Entz-Werle Dr Damien Reita Dr Nelly Etienne-Selloum Dr Véronique Bruban Dr Laurence Choulier Dr Sophie Martin Dr Monique Dontenwill |
| Affiliation: | 1. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France
Cancer and Diabetic Research Group, Department of Biochemistry and Molecular Biology, Faculty of Science, Federal University Ndufu-Alike Ikwo, P.M.B, 1010 Abakaliki, Ebonyi State, Nigeria These authors contributed equally to this work.;2. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France Institut Pluridisciplinaire Hubert Curien (IPHC), UMR CNRS 7178, Université de Strasbourg, 67000 Strasbourg, France These authors contributed equally to this work.;3. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France;4. Institut Pluridisciplinaire Hubert Curien (IPHC), UMR CNRS 7178, Université de Strasbourg, 67000 Strasbourg, France;5. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France Pediatric Onco-Hematology Department, Pediatrics, University Hospital of Strasbourg, 1 avenue Molière, 67098 Strasbourg, France;6. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France Department of Oncobiology, Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, France;7. Laboratoire de Bioimagerie et Pathologies (LBP), UMR CNRS 7021, Institut Thématique Interdisciplinaire InnoVec, Université de Strasbourg, Faculté de Pharmacie, 74 route du, Rhin, CS 60024, 67401 Illkirch Cedex, France Institut du Cancer Strasbourg Europe (ICANS), Service de Pharmacie, 17 rue Albert Calmette, 67200 Strasbourg, France |
| Abstract: | Integrins are heterodimeric transmembrane proteins able to connect cells with the micro-environment. They represent a family of receptors involved in almost all the hallmarks of cancer. Integrins recognizing the Arg-Gly-Asp (RGD) peptide in their natural extracellular matrix ligands have been particularly investigated as tumoral therapeutic targets. In the last 30 years, intense research has been dedicated to designing specific RGD-like ligands able to discriminate selectively the different RGD-recognizing integrins. Chemists′ efforts have led to the proposition of modified peptide or peptidomimetic libraries to be used for tumor targeting and/or tumor imaging. Here we review, from the biological point of view, the rationale underlying the need to clearly delineate each RGD-integrin subtype by selective tools. We describe the complex roles of RGD-integrins (mainly the most studied αvβ3 and α5β1 integrins) in tumors, the steps towards selective ligands and the current usefulness of such ligands. Although the impact of integrins in cancer is well acknowledged, the biological characteristics of each integrin subtype in a specific tumor are far from being completely resolved. Selective ligands might help us to reconsider integrins as therapeutic targets in specific clinical settings. |
| Keywords: | Cancer inhibitors ligand design peptides RGD-integrins |