title: Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model.
abstract: Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial-mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: F-Y
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: B-S
authors.initials: BS
authors.lastname: Wang
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: L-T
authors.initials: LT
authors.lastname: Lin
authors.affiliation: Division of Radiation Oncology, Taipei City Hospital RenAi Branch, Taipei, Taiwan.
authors.forename: J-D
authors.initials: JD
authors.lastname: Leu
authors.affiliation: Department of Life Sciences, TzuChi University, Hualien, Taiwan.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, Taipei 11114, Taiwan.
authors.forename: F-D
authors.initials: FD
authors.lastname: Chen
authors.affiliation: 1] Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan [2] Division of Radiation Oncology, Taipei City Hospital RenAi Branch, Taipei, Taiwan [3] Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Biophotonics Research Laboratory, Department of Engineering and Physics, University of Central Oklahoma, Edmond, OK 73034, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Chen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D017930:Genes, Reporter; D057086:High-Intensity Focused Ultrasound Ablation; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C121252:glycated chitosan; D048271:Chitosan
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