Dendritic cells in tumor microenvironment promoted the neuropathic pain via paracrine inflammatory and growth factors

Abstract

Neuropathic pain associated with cancers was caused by tumor itself or tumor therapy, which was aggravated by sensitizing nociceptor sensory neurons. The tumor microenvironment contributed to tumorigenesis, tumor progress, tumor metastasis, tumor immune resistance, tumor chemotherapy, and tumor immunotherapy. In the current study, we explored the contributions of the infiltrated dendritic cells insulted by Wnt1 in tumor microenvironment to neuropathic pain associated with cancers. The different transcriptome of infiltrated dendritic cells from lung adenocarcinoma and from juxtatumor indicated that thousands of genes were up-regulated by the tumor microenvironment, some of which were enriched in pain pathway. The paracrine factors such as TNF, WNT10A, PDGFA, and NRG1 were also elevated in tumor-infiltrating dendritic cells. The receptors of paracrine factors were highly expressed on dorsal root ganglia (DRG), and not altered in pain conditions. Single-cell RNA-seq data unveiled that TNFSF1 was expressed in neurons, microglial cells, and endothelial cells. PDGFRA was only expressed in microglial cells. ERBB3 was only expressed in neurons. FZD1 and 3 were extensively expressed in various cells. The components composed of signaling pathways associated with the above paracrine factors participated in pain networks. The transcription factors activated by paracrine factor signaling regulated the expression of genes associated with pain. TNF, WNT10A, and PDGFA were extensively expressed in multiple cancers, but their expression in patients did not distribute normally. These data indicated that infiltrated dendritic cells in tumor microenvironment promoted neuropathic pain by sensitizing nociceptor sensory neurons via paracrine factors. Blockage of paracrine factor signaling might alleviate cancer pain.

Screening of disease-related biomarkers related to neuropathic pain (NP) after spinal cord injury (SCI)

“…Tumor-related studies have shown that the upregulation of factor E2F1 can cause pathological pain. The paracrine factors interacting with their receptors could cause the activation of downstream transcription factors such as E2F1 to upregulated expression of genes associated with pain [29]. Studies have shown that factor MITF can promote and survive osteoclast precursors, greatly enhancing the incidence of bone metastasis pain [30].…”

Prognostic Value and Immunological Role of MORF4-Related Gene-Binding Protein in Human Cancers

“…Tumor cells, which usually colonize normal tissues, can form a tumor microenvironment (TME) together with stromal cells, immune cells and their secretory factors and extracellular matrix (ECM) components. Studies have shown that immune cells and the cytokines produced by them, including immunosuppressive and inflammatory cytokines, play a dual role in promoting or preventing cancer development ( Junttila and de Sauvage, 2013 ; Lianyuan et al, 2018 ; Wang et al, 2020 ). Nevertheless, few studies have been conducted on the role of MRGBP in the immune microenvironment.…”

LncRNA CRNDE exacerbates neuropathic pain in chronic constriction injury-induced(CCI) rats through regulating miR-146a-5p/WNT5A pathway

“…Hence, it is important to better understand the molecular mechanisms underlying NP. To simulate NP in vivo, animal experiments commonly use the method of direct nerve damage, especially to the sciatic nerve [2,[25][26][27]. Considering the involvement of lncRNAs in the pathophysiological process of NP, a rat model of NP induced by CCI was adopted in the current study to comprehensively clarify the characteristics and regulatory mechanisms of lncRNAs in NP development.…”

“…Neuropathic pain (NP) is recognized as a kind of chronic pain which is persistent regular pain and leads to 11-19% of incidence in adult population [1,2]. NP is a significantly complex pain disorder arising from abnormalities in the somatosensory nervous system, reducing the life quality of patients and triggering their financial and mental burden [3][4][5].…”