Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers

Abstract

Background and Aim:The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor-associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs. Methods: Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin-8, IL-8) and matrix metalloproteinase-9 (MMP-9) was performed using primary T1 CRCs (n = 49). The HL-60 human promyelocytic leukemia cell line and THP-1 human monocytic leukemia cell line were used to obtain neutrophil-like and macrophage-like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT-PCR was used to analyze gene expression. Results: Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1-positive invasive front of T1 CRCs. Experiments using HL-60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP-9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8-or MMP-9-positive neutrophils at the SAA1-positive invasive front of T1 CRCs. Moreover, co-culture experiments using CRC, THP-1 and HL-60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP-9 in neutrophils. Conclusions: Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

Bioinformatic analysis of underlying mechanisms of Kawasaki disease via Weighted Gene Correlation Network Analysis (WGCNA) and the Least Absolute Shrinkage and Selection Operator method (LASSO) regression model

“…The fractions of memory B cells, plasma cells, CD8 + T cells, CD4 + naïve T cells, CD4 + resting memory T cells, CD4 + activated memory T cells, resting NK cells, activated NK cells, M2 macrophages, resting dendritic cells and resting mast cells were decreased in KDs, which has been demonstrated in several studies [13,[69][70][71][72]. Furthermore, by performing correlation analysis between node genes and immune cells, we discovered that all the node genes have correlation with neutrophils, which has been demonstrated in previous studies [73][74][75][76][77]. Therefore, we can infer that the five-gene signature is involved in the Target miRNAs and the target lncRNAs of these miR-NAs were predicted for the node genes, which may reveal the mechanism through which the node genes are adjusted at the transcriptome level.…”

The role of innate immune cells in the colorectal cancer tumor microenvironment and advances in anti-tumor therapy research

“…They inhibit colon cancer tumor-infiltrating T cells through matrix metalloproteinase (MMP)-mediated activation of transforming factor β (TGFβ) ( 67 ). Some evidence suggests that interactions between macrophages and CRC cells lead to neutrophil recruitment and that SAA1 secreted by CRC cells activates neutrophils to promote invasion ( 68 ). Neutrophil extracellular traps (NETs) play a crucial role in promoting cancer growth by inhibiting T-cell responses through metabolic and functional depletion ( 61 ).…”

SAA1 identified as a potential prediction biomarker for metastasis of hepatocellular carcinoma via multi-omics approaches

“…Moreover, the up-regulation of SAA1 could be used as a predictor and prognostic biomarker for a variety of malignant tumors ( 21 – 24 ). For example, SAA1 produced by colorectal cancer cells recruits neutrophils to the invasive front of colorectal cancer, and stimulates neutrophils to produce CXCL8 and MMP-9, which contribute to tumor progression ( 25 ). In addition, tumor‐associated macrophages promote aggressive behavior by colorectal cancer cells through upregulation of SAA1 via IL‐1β signaling ( 26 ).…”