Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure–Activity Relationship Studies
Thomas Denèfle
(1, 2)
,
Héloise Boullet
(2, 1)
,
Linda Herbi
(2, 3, 4)
,
Clara Newton
(1, 2)
,
Ana-Carolina Martinez-Torres
(4, 2, 3)
,
Alexandre Guez
(2, 1)
,
Elodie Pramil
(2, 1, 3, 4)
,
Claire Quiney
(2, 3, 4)
,
Marilyne Pourcelot
(1, 2)
,
Mikail D. Levasseur
(1, 2)
,
Eva Lardé
(1, 2)
,
Roba Moumné
(2, 1)
,
François-Xavier Ogi
(5)
,
Pascal Grondin
(6)
,
Hélène Merle-Beral
(2, 3, 7)
,
Olivier Lequin
(2, 1)
,
Santos A. Susin
(2, 3, 4)
,
Philippe Karoyan
(1, 2)
Olivier Lequin
- Fonction : Auteur
- PersonId : 760055
- ORCID : 0000-0001-5307-3068
- IdRef : 127152601
Santos A. Susin
- Fonction : Auteur
- PersonId : 739916
- IdHAL : santos-susin
- ORCID : 0000-0002-3366-1628
- IdRef : 111341566
Résumé
Abstract Image
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.