Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8434734 | Cancer Letters | 2018 | 31 Pages |
Abstract
Interferon γ-induced protein 10â¯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.
Keywords
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Cancer Research
Authors
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari,