A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer

Abstract

Background Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells. Methods Immunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo. Results The clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues. Conclusions Our results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer.

Causal inference of the effect of inflammatory cytokines on the risk of oral cancer：two-sample Mendelian randomization

“…Studies have shown elevated NGF expression in oral cancer tissues compared to healthy mucosa. Higher NGF levels have also been associated with increased proliferation and migration in oral cancer cell lines.In pancreatic cancer,NGF could encourage the neuroinvasive potential of pancreatic cancer cells [34] ,and treatment targeting nerve growth factor (NGF) and autophagy pathways may inhibit peripheral nerve in ltration and provide new research directions and an experimental basis for understanding and treating this process [35] . A study [36] initially examinied the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete NGF, which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP)…”

Hawthorn Proanthocyanidin Extract Inhibits Colorectal Carcinoma Metastasis by Targeting the Epithelial-Mesenchymal Transition Process and Wnt/β-Catenin Signaling Pathway

“…Transwell assay was conducted to assess the migration and invasion capacities of HCT116 cells [32]. Following drug pretreatment, the cells (1 × 10 5 cells/well) were resuspended in 200 µL of DMEM without serum and then positioned in the upper chamber.…”

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

“…In xenograft mouse models of TNBC, treatment with anthracycline was evidenced to increase sympathetic nerve fiber activity and norepinephrine concentration in mammary tumors through the induction of nerve growth factor (NGF) by tumor cells, thus driving metastasis [ 322 ]. Cancer exosomes have been demonstrated to induce tumor innervation [ 323 ], and a reciprocal feedback between colon cancer cells and schwann cells mediated by exosomes were also reported to promote the proliferation and metastasis of colon cancer [ 324 ]. More recently, neurotransmitter gamma-amino butyric acid (GABA) induced by sleep deprivation was shown to promote the metastasis of colon cancer through miR‑223‑3p endogenous pathway and exosome pathway [ 325 ].…”