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Oncoprotein GT198 vaccination delays tumor growth in MMTV-PyMT mice.

Authors
  • Achyut, Bhagelu R1
  • Zhang, Hao2
  • Angara, Kartik1
  • Mivechi, Nahid F3
  • Arbab, Ali S1
  • Ko, Lan4
  • 1 Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA. , (Georgia)
  • 2 Department of General Surgery, The First of Affiliated Hospital of Jinan University, And Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China; Research Center of Translational Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China. Electronic address: [email protected] , (China)
  • 3 Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Radiation Oncology, Medical College of Georgia, Augusta University, Augusta, GA, USA. , (Georgia)
  • 4 Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA, USA. Electronic address: [email protected] , (Georgia)
Type
Published Article
Journal
Cancer letters
Publication Date
Apr 28, 2020
Volume
476
Pages
57–66
Identifiers
DOI: 10.1016/j.canlet.2020.02.005
PMID: 32061755
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Targeting early lesion in breast cancer is more therapeutically effective. We have previously identified an oncoprotein GT198 (PSMC3IP) in human breast cancer. Here we investigated GT198 in MMTV-PyMT mouse mammary gland tumors and found that GT198 is a shared early lesion in both species. Similar to human breast cancer even before a tumor appears, cytoplasmic GT198 is overexpressed in mouse tumor stroma including pericyte stem cells, descendent adipocytes, fibroblasts, and myoepithelial cells. Using recombinant GT198 protein as an antigen, we vaccinated MMTV-PyMT mice and found that the GT198 vaccine delayed mouse tumor growth and reduced lung metastasis. The antitumor effects were linearly correlated with vaccinated mouse serum titers of GT198 antibody, which recognized cell surface GT198 protein on viable tumor cells confirmed by FACS. Furthermore, GT198+ tumor cells isolated from MMTV-PyMT tumor induced faster tumor growths than GT198- cells when re-implanted into normal FVB/N mice. Together, this first study of GT198 vaccine in mouse showed its effectiveness in antitumor and anti-metastasis. The finding supports GT198 as a potential target in human immunotherapy since GT198 defect is shared in both human and mouse. Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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