Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39168103.
- Also identified by DOI 10.1016/j.xcrm.2024.101685 and PMC identifier 11384958.
- Licence recorded as CC BY-NC-ND.
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.
Medical subject headings
- Gemcitabine
- Deoxycytidine
- TNF-Related Apoptosis-Inducing Ligand
- Pancreatic Neoplasms
- Mesenchymal Stem Cells
- Carcinoma, Pancreatic Ductal