AUTHOR=Wang Yuanyuan , Zeng Yanqiong , Zhu Linyu , Wan Jiajia , Lei Ningjing , Yao Xiaohan , Duan Xixi , Zhang Yana , Cheng Yanru , Tao Ning , Qin Zhihai 

TITLE=Polysaccharides From Lentinus Edodes Inhibits Lymphangiogenesis via the Toll-Like Receptor 4/JNK Pathway of Cancer-Associated Fibroblasts

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.547683

DOI=10.3389/fonc.2020.547683

ISSN=2234-943X

ABSTRACT=<p>Polysaccharides from <italic>Lentinus edodes</italic> (<italic>L. edodes</italic>) have been successfully used as adjuvant chemotherapy drug to treat lymphatic metastasis in some malignancies, such as colorectal cancer (CRC), lung cancer and gastric cancer. The CRC could metastasize <italic>via</italic> lymphatic vessels. Lymphatic metastasis is commonly thought to be the cause of poor prognosis of CRC. The mechanism of polysaccharides from <italic>L. edodes</italic> inhibiting lymphatic metastasis of CRC is still unclear. In this study, we explored how MPSSS, a novel polysaccharide component of <italic>L. edodes</italic>, influences lymphangiogenesis and lymph node metastasis. The results show that MPSSS can reduce lymphangiogenesis and lymphatic metastasis of CRC in mouse model. And combined with <italic>in vitro</italic> study, a likely mechanism is that MPSSS reduce the secretion of VEGF-C by cancer associated fibroblasts (CAFs). This effect can be suppressed by a TLR4 inhibitor, which suggests that MPSSS plays a role in CAFs through the TLR4/JNK signaling pathway. In conclusion, MPSSS may reduce lymphangiogenesis by decreasing the VEGF-C secretion of CAFs, which may provide a new strategy for the comprehensive treatment of CRC.</p>