Abstract
The polysaccharides MPSSS was extracted from Lentinus edodes and has been reported to effectively inhibit tumor growth and eliminate the function of myeloid-derived immune suppressor cell-mediated T cell inhibition, thus improving the efficacy of cancer therapy. The exploration of how MPSSS affects the functions of cancer-associated fibroblasts (CAFs) will provide a new perspective for understanding the antitumor effects of MPSSS. In the present study, prostate CAFs were selected as target cells to study whether MPSSS affected cell proliferation and function. The results showed that MPSSS did not directly inhibit the growth of prostate CAFs but interfered with CAF-mediated T cell inhibition and affected the immunosuppressive function of prostate CAFs. Mechanistic studies were further performed and showed that MPSSS activated key node proteins in the NF-κB pathway that were dependent on MyD88, and a TLR4 inhibitor blocked the changes in these proteins and the effect of MPSSS. We hypothesize that MPSSS can activate the MyD88-dependent TLR4-NF-κB signaling pathway to change the function of CAFs. In conclusion, these results demonstrate that MPSSS can not only effectively inhibit the growth of prostate cancer as we previously reported but also alter the function of prostate CAFs by activating the TLR4-NF-κB pathway, providing a new strategy for the comprehensive treatment of tumors.
Highlights
Prostate cancer is a cutaneous malignancy that occurs in the prostate and may spread from the prostate to other areas of the body, especially to the bones and lymph nodes [1]
The results showed that there were no significant differences in the viability of prostate cancer-associated fibroblast (CAF) after treatment with MPSSS for 24 h (Figure 1A)
When the incubation time was prolonged to 48 h, there were still no significant differences in the cell activity (Figure 1B), indicating that MPSSS exerts no toxicity in prostate CAFs
Summary
Prostate cancer is a cutaneous malignancy that occurs in the prostate and may spread from the prostate to other areas of the body, especially to the bones and lymph nodes [1]. The treatment of prostate cancer is currently an important topic in biomedical engineering [2]. The occurrence and progression of cancer have been attributed to malignant cells that have ability to proliferate, invade, and metastasize. Studies have shown that tumor progression is not entirely dependent on the accumulation of cancer cells with gene mutations and the tumor microenvironment plays an important role [3]. Fibroblasts, endothelial cells, and immune cells are the main cell types in the tumor microenvironment and are usually immunosuppressive; tumor cells can escape the body’s immune defense and can rapidly grow and spread. As one of the main components in the tumor microenvironment, the matrix encapsulates tumor cells and forms a network of connective tissues around the tumor
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