Open Access

Synergistic inhibitory effects of an engineered antibody‑like molecule ATF‑Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model

  • Authors:
    • Hongwei Zhou
    • Hongwei Wang
    • Guangyuan Yu
    • Zhihong Wang
    • Xi Zheng
    • Haifeng Duan
    • Junzhong Sun
  • View Affiliations

  • Published online on: September 6, 2017     https://doi.org/10.3892/ol.2017.6896
  • Pages: 5189-5196
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The overexpression of the oncogene human epidermal growth factor receptor 2 (HER‑2) has been associated with decreased disease‑free survival and is a marker of poor prognosis of invasive breast cancer. Although the high efficacy of trastuzumab, a drug that targets the HER‑2 oncogene, has been widely recognized, the efficiency of the treatment remains at ~30%. Therefore, novel effective treatments are required for patients with recurrent metastatic breast cancer. The present study aimed to investigate the effects of an engineered antibody‑like molecule administered alone or in combination with trastuzumab on the tumor growth and metastasis of HER‑2‑positive breast cancer. Another aim was to investigate novel cancer therapies for HER‑2‑positive breast cancer. The engineered antibody‑like molecule consists of the amino‑terminal fragment (ATF) of human urokinase‑type plasminogen (uPA) and is conjugated with the Fc fragment of human immunoglobulin G1 (ATF‑Fc). The anti‑cancer effect of ATF‑Fc (alone and in combination with trastuzumab) on tumor cells and in a nude mouse tumor model was evaluated by detecting the expression of uPA, urokinase plasminogen activator receptor (uPAR) and HER‑2. In vitro experiments demonstrated that specifically blocking the uPA‑uPAR and HER‑2 signaling pathways may effectively promote the apoptosis of breast cancer cells. Additionally, ATF‑Fc‑induced cell death in HER‑2‑positive breast cancer cells was observed in vivo. When ATF‑Fc was administered in combination with trastuzumab, cell death was increased and breast cancer metastasis was reduced. The novel engineered antibody‑like molecule ATF‑Fc was able to inhibit HER‑2‑positive breast cancer cell growth and metastasis by interfering with uPA and its receptor (uPA‑uPAR) system. Additionally, the antibody‑like molecule exhibits a synergistic inhibitory effect when administered in combination with trastuzumab.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhou H, Wang H, Yu G, Wang Z, Zheng X, Duan H and Sun J: Synergistic inhibitory effects of an engineered antibody‑like molecule ATF‑Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model. Oncol Lett 14: 5189-5196, 2017
APA
Zhou, H., Wang, H., Yu, G., Wang, Z., Zheng, X., Duan, H., & Sun, J. (2017). Synergistic inhibitory effects of an engineered antibody‑like molecule ATF‑Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model. Oncology Letters, 14, 5189-5196. https://doi.org/10.3892/ol.2017.6896
MLA
Zhou, H., Wang, H., Yu, G., Wang, Z., Zheng, X., Duan, H., Sun, J."Synergistic inhibitory effects of an engineered antibody‑like molecule ATF‑Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model". Oncology Letters 14.5 (2017): 5189-5196.
Chicago
Zhou, H., Wang, H., Yu, G., Wang, Z., Zheng, X., Duan, H., Sun, J."Synergistic inhibitory effects of an engineered antibody‑like molecule ATF‑Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model". Oncology Letters 14, no. 5 (2017): 5189-5196. https://doi.org/10.3892/ol.2017.6896