A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro

  • Authors:
    • Le-Qun Shan
    • Sai Ma
    • Xiu-Chun Qiu
    • Tao Wang
    • Shi-Bin Yu
    • Bao-An Ma
    • Yong Zhou
    • Qing-Yu Fan
    • An-Gang Yang
  • View Affiliations

  • Published online on: December 7, 2010     https://doi.org/10.3892/or.2010.1074
  • Pages: 325-331
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Abstract

Immunotherapy is a promising strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive tumors. Previously, we constructed an immuno-carboxy terminal fragment of Bid (immuno-tBid) and reported its specific and effective destruction of HER2-positive tumor cells. In this study, in order to further reduce the immunogenicity of the previous immuno-proapoptotic protein, we constructed a novel immuno-tBid by replacing domain II of Pseudomonas exotoxin A with a short furin cleavage sequence from the diphtheria toxin. In order to explore the possible application of this novel immuno-tBid in the treatment of osteosarcoma, we first examined the expression of the HER2 protein in a subclone of a human osteosarcoma cell line with relatively high metastatic potential (SOSP-9607-E10), as well as in clinical specimens of osteosarcoma. Quantitative real-time PCR and Western blot analysis revealed that the expression of HER2 was up-regulated in the SOSP-9607-E10 cells, while immunohistochemical analysis revealed that HER2 was overexpressed in 37% of the tissue specimens examined. Both HER2-positive SOSP-9607-E10 and SKBR-3 cells, as well as HER2-negative HeLa cells were transiently transfected with the novel immuno-tBid in order to study its specific pro-apoptotic effect. We demonstrate here that this novel immuno-tBid induces the specific destruction of HER2-overexpressing SOSP-9607-E10 cells through the release of cytochrome C. These results suggest that the novel immuno-tBid with a minimized exogenous fragment could represent a competitive approach for the treatment of HER2-positive osteosarcoma.

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February 2011
Volume 25 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Shan L, Ma S, Qiu X, Wang T, Yu S, Ma B, Zhou Y, Fan Q and Yang A: A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro. Oncol Rep 25: 325-331, 2011
APA
Shan, L., Ma, S., Qiu, X., Wang, T., Yu, S., Ma, B. ... Yang, A. (2011). A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro. Oncology Reports, 25, 325-331. https://doi.org/10.3892/or.2010.1074
MLA
Shan, L., Ma, S., Qiu, X., Wang, T., Yu, S., Ma, B., Zhou, Y., Fan, Q., Yang, A."A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro". Oncology Reports 25.2 (2011): 325-331.
Chicago
Shan, L., Ma, S., Qiu, X., Wang, T., Yu, S., Ma, B., Zhou, Y., Fan, Q., Yang, A."A novel recombinant immuno-tBid with a furin site effectively suppresses the growth of HER2-positive osteosarcoma cells in vitro". Oncology Reports 25, no. 2 (2011): 325-331. https://doi.org/10.3892/or.2010.1074