Xin He1, Xiaoguang Ma2, Congcong Wang1, Mingchun Luan1, Ying Li3, Xiaohua Huang4, Keli Ma5. 1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China. 2. Department of Respirotory and Clinical Medecine, First Affiliated Hospital of Dalian Medical University, Dalian, China. 3. Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, China. 4. Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian, China. xiaohua312@sina.com. 5. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China. makelipaper@163.com.
Abstract
BACKGROUND: Tetraspanin KAI1/CD82, a tumor metastasis suppressor, has emerged as a promising molecular target for the management of metastatic disease. However, the peptide mimicking small extracellular ring domain (EC1) of CD82 has not been fully investigated for the function of inhibiting cell migration in vitro and tumor metastasis in vivo. METHODS: Different cancer cells were treated with EC1 mimic peptide in order to detect migration and invasion by the healing assay and transwell. Cell aggregation and adhesion assays were used to investigate the function of homotypic cell-cell aggregation and adhesion to tissue culture plates. Then, we established syngeneic and xenograft animal models to assess the metastasis inhibitory effect of EC1 mimic peptide in vivo. RESULTS: In vitro studies, the EC1 mimic peptide had been showed to promote homotypic cell-cell aggregation, suppress cell migration, invasion and adherence in multiple tumor cell types. In vivo metastasis assays, the EC1 mimic peptide could strongly inhibit the pulmonary metastasis of LCC in syngeneic mice model and SW620 and H1299 in xenograft mice model. CONCLUSION: This novel finding will improve our understanding of the mechanism by which CD82 inhibits metastasis, and suggests that EC1 mimic peptide may be a promising candidate for developing anti-metastasis drugs.
BACKGROUND: Tetraspanin KAI1/CD82, a tumor metastasis suppressor, has emerged as a promising molecular target for the management of metastatic disease. However, the peptide mimicking small extracellular ring domain (EC1) of CD82 has not been fully investigated for the function of inhibiting cell migration in vitro and tumor metastasis in vivo. METHODS: Different cancer cells were treated with EC1 mimic peptide in order to detect migration and invasion by the healing assay and transwell. Cell aggregation and adhesion assays were used to investigate the function of homotypic cell-cell aggregation and adhesion to tissue culture plates. Then, we established syngeneic and xenograft animal models to assess the metastasis inhibitory effect of EC1 mimic peptide in vivo. RESULTS: In vitro studies, the EC1 mimic peptide had been showed to promote homotypic cell-cell aggregation, suppress cell migration, invasion and adherence in multiple tumor cell types. In vivo metastasis assays, the EC1 mimic peptide could strongly inhibit the pulmonary metastasis of LCC in syngeneic mice model and SW620 and H1299 in xenograft mice model. CONCLUSION: This novel finding will improve our understanding of the mechanism by which CD82 inhibits metastasis, and suggests that EC1 mimic peptide may be a promising candidate for developing anti-metastasis drugs.