Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Biosci Rep. 2019 May 10;39(5). doi: 10.1042/BSR20182171. Print 2019 May 31.
The polysaccharides MPSSS was extracted from 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.
从 中提取的多糖 MPSSS 已被报道能有效地抑制肿瘤生长并消除髓源性免疫抑制细胞介导的 T 细胞抑制功能，从而提高癌症治疗的疗效。探索 MPSSS 如何影响癌症相关成纤维细胞（CAFs）的功能，将为理解 MPSSS 的抗肿瘤作用提供新视角。在本研究中，选择前列腺 CAFs 作为靶细胞，研究 MPSSS 是否影响细胞增殖和功能。结果表明，MPSSS 并不直接抑制前列腺 CAFs 的生长，而是干扰 CAF 介导的 T 细胞抑制作用，并影响前列腺 CAFs 的免疫抑制功能。进一步的机制研究表明，MPSSS 激活了 NF-κB 通路中的关键节点蛋白，该过程依赖于 MyD88，TLR4 抑制剂阻断了这些蛋白的变化以及 MPSSS 的作用。我们假设 MPSSS 可以通过激活 MyD88 依赖性 TLR4-NF-κB 信号通路来改变 CAFs 的功能。总之，这些结果表明，MPSSS 不仅能像我们之前报道的那样有效地抑制前列腺癌的生长，而且能通过激活 TLR4-NF-κB 通路改变前列腺 CAFs 的功能，为肿瘤的综合治疗提供了新策略。
