Restoration of stemness-high tumor cell-mediated suppression of murine dendritic cell activity and inhibition of tumor growth by low molecular weight oyster polysaccharide

Abstract

Dendritic cells (DCs) play key regulatory roles in tumor immunity: increased activity of DCs infiltrating tumor tissues leads to enhancement of tumor immunity. Functions of DCs are also modulated by tumor cell-derived factors. Here, we investigated the effects of low molecular weight oyster polysaccharide (LMW-OPS) on differentiation and function of bone marrow-derived DCs (BMDCs) exposed to a conditioned medium (CM) obtained from spheres of stemness-high colorectal cancer cell lines CMT93 and CT26. The CM containing a detectable level of TGF-β1 was found to down-regulate the surface expression of major histocompatibility complex class II of BMDCs and to inhibit the potency of BMDCs to stimulate T cells. Those suppressions were partly restored and completely restored by addition of anti-TGF-β1 and LMW-OPS, respectively. Production of IFN-γ during allogeneic T cell responses was inhibited by the CM, whereas production of TGF-β1 was augmented by the CM. The IFN-γ profile was also reversed by addition of LMW-OPS. Nuclear translocation of β-catenin, but not that of NF-κB p65, was induced by TGF-β1. NF-κB p65 nuclear translocation, but not β-catenin nuclear translocation, was induced by LMW-OPS. Intraperitoneal injection of LMW-OPS significantly suppressed tumor growth in syngeneic tumor models using CMT93 and CT26 sphere cells, whereas it had no inhibitory effect on the proliferation of either cell line. The results demonstrated that LMW-OPS relieved stemness-high tumor cell-mediated suppression of BMDC function and indicated the in vivo anti-tumor activity of LMW-OPS in which re-stimulation of the activity of DCs infiltrating tumor tissues is presumed to be involved.

Keywords: Colorectal cancer stem cells; Dendritic cells; NF-κB; Oyster polysaccharide; TGF-β.