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- Title
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
- 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.
- Subjects
TRASTUZUMAB; TUMOR growth; CANCER invasiveness; BREAST cancer surgery; XENOGRAFTS; GENETIC overexpression; LABORATORY mice; THERAPEUTICS
- Publication
Oncology Letters, 2017, Vol 14, Issue 5, p5189
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2017.6896