A novel cancer therapeutic using thrombospondin 1 in dendritic cells

Tzu Yang Weng, Shih Shien Huang, Meng Chi Yen, Chi Chen Lin, Yi Ling Chen, Chiu Mei Lin, Wei Ching Chen, Chih Yang Wang, Jang Yang Chang, Ming Derg Lai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in dendritic cells (DCs) influences tumor progression. We investigated tumor growth and immune mechanism by downregulation of TSP-1 in dendritic cells. Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced anticancer therapeutic effects. Tumor-infiltrating CD4 + and CD8 + T cells were increased after the administration of TSP-1 shRNA. The expression of interleukin-12 and interferon-γ in the lymph nodes was enhanced by injection of TSP-1 shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of CD8 + T cells. Injection of CD11c + TSP-1-knockout (TSP-1-KO) bone marrow-derived DCs (BMDCs) delayed tumor growth in tumor-bearing mice. Similarly, antitumor activity induced by TSP-1-KO BMDCs was abrogated by depletion of CD8 + T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1 shRNA functioned as an immunotherapeutic adjuvant to augment the therapeutic efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs produces an effective antitumor response that is opposite to the protumor effects by silencing of TSP-1 within tumor cells.

Original languageEnglish
Pages (from-to)292-302
Number of pages11
JournalMolecular Therapy
Volume22
Issue number2
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Pathologic Neovascularization
Thrombospondin 1
Thrombospondins
Animal Disease Models
Cancer Vaccines
DNA Vaccines
Gene Silencing
Tumor Cell Line
Cellular Immunity
Genetic Therapy
Immunotherapy
Dendritic Cells
Small Interfering RNA
Skin
Neoplasms
Therapeutics
T-Lymphocytes
Down-Regulation
Growth
Bone Marrow

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Weng, T. Y., Huang, S. S., Yen, M. C., Lin, C. C., Chen, Y. L., Lin, C. M., ... Lai, M. D. (2014). A novel cancer therapeutic using thrombospondin 1 in dendritic cells. Molecular Therapy, 22(2), 292-302. https://doi.org/10.1038/mt.2013.236

A novel cancer therapeutic using thrombospondin 1 in dendritic cells. / Weng, Tzu Yang; Huang, Shih Shien; Yen, Meng Chi; Lin, Chi Chen; Chen, Yi Ling; Lin, Chiu Mei; Chen, Wei Ching; Wang, Chih Yang; Chang, Jang Yang; Lai, Ming Derg.

In: Molecular Therapy, Vol. 22, No. 2, 01.01.2014, p. 292-302.

Research output: Contribution to journalArticle

Weng, TY, Huang, SS, Yen, MC, Lin, CC, Chen, YL, Lin, CM, Chen, WC, Wang, CY, Chang, JY & Lai, MD 2014, 'A novel cancer therapeutic using thrombospondin 1 in dendritic cells', Molecular Therapy, vol. 22, no. 2, pp. 292-302. https://doi.org/10.1038/mt.2013.236
Weng TY, Huang SS, Yen MC, Lin CC, Chen YL, Lin CM et al. A novel cancer therapeutic using thrombospondin 1 in dendritic cells. Molecular Therapy. 2014 Jan 1;22(2):292-302. https://doi.org/10.1038/mt.2013.236
Weng, Tzu Yang ; Huang, Shih Shien ; Yen, Meng Chi ; Lin, Chi Chen ; Chen, Yi Ling ; Lin, Chiu Mei ; Chen, Wei Ching ; Wang, Chih Yang ; Chang, Jang Yang ; Lai, Ming Derg. / A novel cancer therapeutic using thrombospondin 1 in dendritic cells. In: Molecular Therapy. 2014 ; Vol. 22, No. 2. pp. 292-302.
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