Abstract :
[en] Thrombospondin-1 (TSP-1) is a glycoprotein
considered as a key actor within the tumor microenvironment.
Its binding to CD47, a cell surface receptor, triggers
programmed cell death. Previous studies allowed the
identification of 4N1K decapeptide derived from the TSP-1/
CD47 binding epitope. Here, we demonstrate that this peptide
is able to induce selective apoptosis of various cancer cell lines
while sparing normal cells. A structure−activity relationship study led to the design of the first serum stable TSP-1 mimetic agonist peptide able to trigger selective programmed cell death (PCD) of at least lung, breast, and colorectal cancer cells. Altogether, these results will be of valuable interest for further investigation in the design of potent CD47 agonist peptides, opening new perspectives for the development of original anticancer therapies.
Research Center/Unit :
Sorbonne-Université, UPMC, Université Paris 06, Ecole Normale Supeŕieure, CNRS, Laboratoire des Biomolećules, 75005 Paris, France
Deṕartement de Chimie, Ecole Normale Supeŕieure,PSL Research University, UPMC Université Paris 06, CNRS, Laboratoiredes Biomolećules,75005 Paris, France
Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France
Université Paris Descartes, Sorbonne Paris Cite,́ UMRS 1138, Paris, France
AP-HP, GH Pitie-́Salpet̂rier̀e, Service d’Heḿatologie Biologique, 75013 Paris, France
NanoTemper Technologies GmbH, Floessergasse 4, 81369 Munich, Germany
GSK, 25 Avenue du Queb́ec, 91140 Les Ulis ,France
Scopus citations®
without self-citations
14
