A Therapeutic Strategy for Metastatic Malignant Fibrous Histiocytoma Through Mesenchymal Stromal Cell-Mediated TRAIL Production.
SCIE
SCOPUS
- Title
- A Therapeutic Strategy for Metastatic Malignant Fibrous Histiocytoma Through Mesenchymal Stromal Cell-Mediated TRAIL Production.
- Authors
- Lee, HJ; Yang, HM; Choi, YS; Park, SH; Moon, SH; Lee, YS; Sung, YC; Kim, SJ
- Date Issued
- 2013-05
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Abstract
- Objective: To overcome the therapeutic limitations of malignant fibrous histiocytoma (MFH), we evaluated human adipose tissue-derived mesenchymal stromal cells (MSCs) that secrete tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on metastatic MFH. Background: MFH is a highly malignant and metastatic type of sarcoma but surgical removal is the only effective method for treating MFH. MSCs are easily transduced to express a high level of transgene and can migrate toward cancer. For this reason, MSCs are a promising candidate for metastatic MFH therapies. Methods: In vitro sustainability of MSC-TRAIL against MFH-ino was analyzed by apoptosis assay. For preclinical study, anti-MFH effects of MSC-TRAILs were validated in murine models for local tumorigenesis and metastasis. Furthermore, a time-interval metastasis model of MFH was applied to confirm antimetastatic ability of MSC-TRAIL for preestablished metastatic MFH. Results: We found that MFH-ino is highly susceptible to recombinant TRAIL and MSC-TRAIL, which selectively induce apoptosis via caspase-8 activation in vitro. Moreover, not only MFH-ino but xenograft explants were also significantly inhibited by MSC-TRAIL in local tumorigenesis. In particular, the metastatic ability of MFH-ino was considerably reduced by MSC-TRAIL in metastasis murine model, particularly for preestablished metastatic MFH. Conclusions: These results suggest that MSC-TRAIL is sufficiently effective in inhibiting MFH-ino metastasis and the application using MSC-TRAIL could be extended to other sarcomas and recurrent metastatic cancers for cell-mediated cancer therapy.
- Keywords
- adenoviral transduction; human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs); malignant fibrous histiocytoma (MFH); metastasis; tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL); APOPTOSIS-INDUCING LIGAND; STEM-CELLS; GENE-THERAPY; ADIPOSE-TISSUE; TARGETED-DELIVERY; GLIOMA THERAPY; EWINGS-SARCOMA; CANCER-THERAPY; MOUSE MODELS; TUMOR STROMA
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/15471
- DOI
- 10.1097/SLA.0B013E3182710401
- ISSN
- 0003-4932
- Article Type
- Article
- Citation
- ANNALS OF SURGERY, vol. 257, no. 5, page. 952 - 960, 2013-05
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.