Myxomaviral Anti-Inflammatory Serpin Reduces Myeloid-Derived Suppressor Cells and Human Pancreatic Cancer Cell Growth in Mice

Journal of Cancer Science & Therapy
Donghang ZhengAlexandra R Lucas

Abstract

Modification of the tumor microenvironment by inflammatory cells represents a newly recognized driving force in cancer with critical roles in tumor invasion, growth, angiogenesis, and metastasis. Increased thrombolytic cascade serine proteases, specifically urokinase-type plasminogen activator and its receptor, correlate with inflammatory cell migration, pancreatic cancer growth, invasion and unfavorable outcomes. Inflammation in pancreatic cancer is linked with myeloid-derived suppressor cell (MDSC) activity and cancer progression. Myxomavirus is a complex DNA virus encoding highly potent immune modulators. Serp-1 and M-T7 are two such secreted anti-inflammatory myxomaviral proteins. Serp-1 inhibits uPA, plasmin and coagulation factor X while M-T7 inhibits C, CC, and CXC chemokines. We have explored the potential use of these viral proteins for treatment of a range of human cancer isolates engrafted in severe combined immunodeficient (SCID) mice. Engrafted tumors were treated with either Serp-1, neuroserpin, a related mammalian serpin that inhibits thrombolytic proteases, or M-T7. Serp-1 and neuroserpin inhibited growth of the pancreatic cancer cell line Hs766t (P=0.03 and P=0.01, respectively) at 4 weeks after implantation. S...Continue Reading

Citations

Sep 19, 2016·Seminars in Cell & Developmental Biology·Tet Woo LeeNigel P Birch
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chiyoko NishimeMasatoshi Wakui
Sep 1, 2019·Journal of Clinical Medicine·Ahmed S ElshikhaSihong Song

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Datasets Mentioned

BETA
MDA231

Methods Mentioned

BETA
flow cytometry
Assay
xenograft
xenografts

Software Mentioned

Stat View
SAS
Gatelogic

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