Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer.
Adenocarcinoma
/ pathology
Animals
Apoptosis
Carcinoma, Pancreatic Ductal
/ pathology
Genetic Therapy
Humans
Mesenchymal Stem Cells
/ metabolism
Mice
Pancreatic Neoplasms
/ pathology
Receptors, TNF-Related Apoptosis-Inducing Ligand
/ metabolism
TNF-Related Apoptosis-Inducing Ligand
/ genetics
Xenograft Model Antitumor Assays
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 02 2019
11 02 2019
Historique:
received:
31
08
2017
accepted:
06
12
2018
entrez:
12
2
2019
pubmed:
12
2
2019
medline:
22
9
2020
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.
Identifiants
pubmed: 30742129
doi: 10.1038/s41598-018-37433-6
pii: 10.1038/s41598-018-37433-6
pmc: PMC6370785
doi:
Substances chimiques
Receptors, TNF-Related Apoptosis-Inducing Ligand
0
TNF-Related Apoptosis-Inducing Ligand
0
TNFSF10 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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