In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factor–related apoptosis inducing ligand in osteosarcoma pre-clinical models

Abstract : In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factorÀrelated apoptosis inducing ligand in osteosarcoma pre-clinical models Abstract Background: Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor. OS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine Tumor necrosis factor (TNF)ÀRelated Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, many OS cell lines appear resistant to recombinant human (rh)TRAIL-induced apoptosis. We, therefore, hypothesized that TRAIL presentation at the membrane level of carrier cells might overcome this resistance and trigger apoptosis. Methods: To address this, human adipose mesenchymal stromal cells (MSCs) transfected in a stable manner to express membrane-bound full-length human TRAIL (mbTRAIL) were co-cultured with several human OS cell lines. Results: This induced apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL. In contrast, mbTRAIL delivered by MSCs was not able to counteract tumor progression in this OS orthotopic model. Discussion: This was partly due to the fact that MSCs showed a potential to support tumor development. Moreover, the expression of mbTRAIL did not show caspase activation in adjacent tumor cells.
Document type :
Journal articles
Complete list of metadatas

Cited literature [28 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01859553
Contributor : Sandrine Maurice <>
Submitted on : Wednesday, August 22, 2018 - 11:41:37 AM
Last modification on : Tuesday, August 6, 2019 - 9:02:16 AM
Long-term archiving on : Friday, November 23, 2018 - 1:52:41 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Romain Guiho, Kevin Biteau, Giulia Grisendi, Mathias Chatelais, Régis Brion, et al.. In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factor–related apoptosis inducing ligand in osteosarcoma pre-clinical models. Cytotherapy, Elsevier, 2018, Epub ahead of print. ⟨10.1016/j.jcyt.2018.06.013⟩. ⟨inserm-01859553⟩

Share

Metrics

Record views

104