The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model

(2018) The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model. Cancer Letters. pp. 30-39. ISSN 0304-3835

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Abstract

Interferon gamma-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. (C) 2018 Elsevier B.V. All rights reserved.

Item Type: Article
Keywords: melanoma metastasis human adipose derived mesenchymal stem cells cxcl10 regulatory t-cells human breast-cancer targeted therapy poor survival gene-transfer delivery recruitment carcinoma ip-10 immunotherapy
Divisions: Faculty of Medicine > Department of Basic Science > Department of Anatomical Sciences
Faculty of Medicine > Department of Basic Science > Department of Molecular Medicine and Genetics
Faculty of Medicine > Department of Basic Science > Department of Parasitology and Mycology
Faculty of Medicine > Departments of Clinical Sciences > Department of Pathology
Page Range: pp. 30-39
Journal or Publication Title: Cancer Letters
Journal Index: ISI
Volume: 419
Identification Number: https://doi.org/10.1016/j.canlet.2018.01.029
ISSN: 0304-3835
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/6773

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