Abstract
Lipopolysaccharide (LPS) exists in the outer membrane of Gram-negative bacteria. Colorectal normal epithelium and colorectal cancer cells in situ are continuously exposed to LPS from intestinal bacteria, while little is known about the influence of LPS on colorectal cancer progression and metastasis. In this study, we investigated the potential role of LPS on colorectal cancer progression and metastasis as well as the underlying mechanisms. We measured higher LPS concentration in colorectal cancer tissues and even higher LPS concentration in colorectal cancer tissues with lymph node metastasis. LPS significantly enhanced cancer cell motility and promoted human dermal lymphatic endothelial cells' (HDLECs') capacity of tube-like formation in vitro, as well as accelerates lymphangiogenesis and lymph node metastasis in nude mice. Furthermore, we demonstrated LPS notably increased the expression of VEGF-C in a time-dependent and concentration-dependent manner. VEGF-C is a key regulator for lymphangiogenesis and lymph node metastasis. By constructing lentivirus-mediated shVEGF-C cells, VEGF-C down-regulation suppressed LPS' promotive effect on cancer cell motility and HDLEC tube-like formation capacity. In addition, we found TLR4- NF-κB/JNK signal pathways were important for LPS to increase VEGF-C expression. All these result suggested a critical role for LPS in migration, invasion, lymphangiogenesis and lymph node metastasis of colorectal cancer, providing evidence that LPS increased VEGF-C secretion to promote cell motility and lymphangiogenesis via TLR4- NF-κB/JNK signaling.
Highlights
Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in the world and the fifth leading cause in China, and the incidence and mortality have a gradually increasing trend [1, 2]
Wound healing assay was consistent with the result (Figure 5E and 5F). These results indicated that LPS enhanced colorectal cancer cell motility was partially caused by VEGF-C
On the basis in vitro, we investigated whether LPS can influence lymphangiogenesis and lymph node metastasis by establishing mice models of colorectal cancer
Summary
Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in the world and the fifth leading cause in China, and the incidence and mortality have a gradually increasing trend [1, 2]. The microbial infection may promote colon cancer metastasis. Bacteria is an important component of the human body, while dysbiotic microbiota may promote disease development and contributes to the progression of colorectal cancer [3, 4]. Previous studies suggested that bacterial infection can activate immune cells to recognize tumor antigen which can cause immune reactions to kill tumor cells [5, 6], but long-term infection can raise inflammatory factors and cells to promote tumor progression and metastasis [7,8,9]. Recent experimental and clinical data showed that besides the inflammatory cytokines, bacteria and their products are important factors to promote tumor progression and metastasis [10, 11]. Exploring the mechanism of intestinal flora promoting colon cancer metastasis, especially the mechanism of lymphatic metastasis [12] and designing effective drug treatment is of great significance to improve survival rates of patients with colorectal cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
