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.