Your browser doesn't support javascript.
loading
Oncolytic Adenovirus rAd.DCN Inhibits Breast Tumor Growth and Lung Metastasis in an Immune-Competent Orthotopic Xenograft Model.
Zhao, Huiqiang; Wang, Hao; Kong, Fanxuan; Xu, Weidong; Wang, Tao; Xiao, Fengjun; Wang, Lisheng; Huang, Dandan; Seth, Prem; Yang, Yuefeng; Wang, Hua.
Afiliação
  • Zhao H; 1 Department of Cadre Health Care, Navy General Hospital, Beijing, P.R. China.
  • Wang H; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
  • Kong F; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
  • Xu W; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
  • Wang T; 3 Gene Therapy Program, Department of Medicine, NorthShore Research Institute, Evanston, Illinois.
  • Xiao F; 4 Breast Cancer Department, PLA 307 Hospital, Beijing, P.R. China.
  • Wang L; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
  • Huang D; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
  • Seth P; 5 Stem Cell Laboratory, Ningbo No. 2 Hospital, Ningbo, P.R. China.
  • Yang Y; 3 Gene Therapy Program, Department of Medicine, NorthShore Research Institute, Evanston, Illinois.
  • Wang H; 2 Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, P.R. China.
Hum Gene Ther ; 30(2): 197-210, 2019 02.
Article em En | MEDLINE | ID: mdl-30032645
ABSTRACT
The majority of advanced breast cancer patients develop distal metastasis, including lung and bone metastasis. However, effective therapeutic strategies to prevent metastasis are still lacking. Decorin is a natural inhibitor of transforming growth factor ß, which plays a pivotal role in tumor metastasis. An oncolytic adenovirus expressing decorin, rAd.DCN, has been developed previously. In an immune-competent breast tumor (4T1) model, intratumoral (i.t.) as well as intravenous (i.v.) delivery of rAd.DCN inhibited growth of orthotopic tumors and spontaneous lung metastasis. It was shown that i.t. delivery of rAd.DCN produced higher levels of transgene expression and evoked stronger oncolysis of the tumors compared to i.v. delivery. However, i.v. delivery resulted in higher amount of virus accumulation in the lungs and produced stronger responses to prevent tumor lung metastasis. Oncolytic adenovirus-mediated decorin expression in the tumors downregulated the decorin target genes and decreased epithelial mesenchymal transition markers. Decorin expression in lung tissues also increased Th1 cytokine expression, such as interleukin (IL)-2, IL-12, and tumor necrosis factor α, and decreased Th2 cytokines, such as transforming growth factor ß and IL-6. Moreover, rAd.DCN treatment induced strong systemic inflammatory responses and upregulated CD8+ T lymphocytes. In conclusion, rAd.DCN inhibits tumor growth and lung metastasis of breast cancer via regulating wnt/ß-catenin, vascular endothelial growth factor (VEGF), and Met pathways, and modulating the antitumor inflammatory and immune responses. Considering that i.v. delivery was much more effective in preventing lung metastasis, systemic delivery of rAd.DCN might be a promising strategy to treat breast cancer lung metastasis.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica / Decorina / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica / Decorina / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article