Activated macrophages promote invasion by early colorectal cancer via an interleukin 1β‐serum amyloid A1 axis

Sudo, Gota; Aoki, Hironori; Yamamoto, Eiko; Takasawa, Akira; Niinuma, Takeshi; Yoshido, Ayano; Kitajima, Hiroshi; Yorozu, Akira; Kubo, Toshiyuki; Harada, Taku; Ishiguro, Kazuya; Kai, Masahiro; Katanuma, Akio; Yamano, Hiro‐o; Osanai, Makoto; Nakase, Hiroshi; Suzuki, Hiromu

doi:10.1111/cas.15080

Cited by 12 publications

(28 citation statements)

References 54 publications

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“…Primary T1 CRCs (n = 49) were collected from Japanese patients at Teine-Keijinkai Hospital and Sapporo Medical University, as described previously. 5 Informed consent was obtained from all patients. Approval for this study was obtained from the Intuitional Review boards of Sapporo Medical University and Teine-Keijinkai Hospital.…”

Section: Methodsmentioning

confidence: 99%

“…6,11 Our earlier results suggest that neutrophils are involved in the progression of SAA1-positive T1 CRCs, but their functional roles and their association with SAA1 remain elusive. 5 In the present study, we aimed to clarify the clinical and biological significance of neutrophils and their relation to SAA1 at the invasive front T1 CRCs.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] In an earlier study, we analyzed the transcriptome of T1b CRC with poorly differentiated components (PORs), which is one of the risk factors for LNM, and found that SAA1 is upregulated in PORs at the invasive front of T1b CRCs. 5 In vitro experiments showed that SAA1 promotes migration and invasion by CRC cells. We also found that CRC cells promote production of interleukin-1β (IL-1β) by macrophages and that this macrophage-derived IL-1β induces SAA1 upregulation in CRC cells.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, immunohistochemical analysis confirmed accumulation of MMP-9positive macrophages and neutrophils at the invasive front of SAA1-positive tumors. 5 The tumor microenvironment, including blood vessels, fibroblasts and macrophages, plays an essential role in promoting the growth of CRC. 6 Likewise, tumor-associated neutrophils (TANs) also play an important role in the progression of CRC.…”

Section: Introductionmentioning

confidence: 99%

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

Yoshido

Sudo

Takasawa

et al. 2022

J of Gastro and Hepatol

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yoshido

Sudo

Takasawa

et al. 2022

J of Gastro and Hepatol

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“…In addition to inducing proliferation and survival of cancer cells, IL-1β can also favor their migration and invasion. In a colorectal cancer (CRC) model, macrophage-derived IL-1β was shown to elicit the production of serum amyloid A1 (SAA1) by tumor cells, which in a feed-forward manner induced macrophages to upregulate metalloproteinase-9 secretion allowing cancer migration and establishment of metastasis ( Sudo et al, 2021 ) ( Figure 2A ). Whereas the bulk of the evidence point to IL-1β as the main driver of inflammasome tumor-promoting effects, a recent study by Hofbauer et al , studying multiple myeloma in a murine model, described a role of Nlrp3-dependent IL-18 in bone destruction and multiple myeloma proliferation ( Hofbauer et al, 2021 ).…”

Section: Protumoral Functions Of the Inflammasome Pathwaymentioning

confidence: 99%

Inflammasomes in Cancer Progression and Anti-Tumor Immunity

Lillo

Saleh

2022

Front. Cell Dev. Biol.

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The inflammasomes are critical regulators of innate immunity, inflammation and cell death and have emerged as important regulators of cancer development and control. Inflammasomes are assembled by pattern recognition receptors (PRR) following the sensing of microbial- or danger-associated molecular patterns (MAMPs/DAMPs) and elicit inflammation through the oligomerization and activation of inflammatory caspases. These cysteinyl-aspartate proteases cleave the proinflammatory cytokines IL-1β and IL-18 into their biologically active mature form. The roles of the inflammasomes and associated pro-inflammatory cytokines vary greatly depending on the cancer type. Here we discuss recent studies highlighting contrasting roles of the inflammasome pathway in curbing versus promoting tumorigenesis. On one hand, the inflammasomes participate in stimulating anti-tumor immunity, but they have also been shown to contribute to immunosuppression or to directly promote tumor cell survival, proliferation, and metastasis. A better understanding of inflammasome functions in different cancers is thus critical for the design of novel cancer immunotherapies.

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CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma

et al. 2022

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Background:The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs.Methods: Publicly available single-cell RNA-sequencing (RNA-seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, αsmooth muscle antigen (α-SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co-cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse-transcription PCR.Results: Analysis of the RNA-seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12-positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α-SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance.CXCL12 was significantly upregulated in muscle cells co-cultured with OSCC cells.

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Activated macrophages promote invasion by early colorectal cancer via an interleukin 1β‐serum amyloid A1 axis

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 12 publications

References 54 publications

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

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

Inflammasomes in Cancer Progression and Anti-Tumor Immunity

CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma

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