NLRP3 inflammasomes in macrophages drive colorectal cancer metastasis to the liver

Deng, Qiaoting; Geng, Yan; Zhao, Liying; Ru, Li; Zhang, Zhigao; Li, Kun; Liang, Rongliang; Shao, Xiangyang; Huang, Mengyi; Zuo, Daming; Wu, Yanni; Ma, Qiang

doi:10.1016/j.canlet.2018.10.030

Cited by 80 publications

(48 citation statements)

References 26 publications

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“…Hepatic metastasis following splenic injection of colon cancer cells is enhanced in Casp1 −/− Casp11 −/− and Nlrp3 −/− mice, which is dependent on IL-18 but not IL-1β 63 . In contrast, a similar study has suggested that NLRP3-dependent IL-1β secretion from macrophages may shift tumor cells to a more migratory phenotype to drive hepatic dissemination and metastasis of colon cancer 64 . However, a critical flaw in the latter study is that different strains of WT and KO mice have been used, which generates difficulty in assessing the contribution of the gene of interest.…”

Section: Metastasismentioning

confidence: 93%

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Diverging inflammasome signals in tumorigenesis and potential targeting

2019

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Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase-1, thereby promoting the secretion of bioactive interleukin-1β and interleukin-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signaling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration, and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis, and metastasis. Conversely, inflammasome signaling also contributes to tumor suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the significance of environmental factors, such as diet and gut microbiota [G] in inflammasome signaling, which in turn influences tumorigenesis. In this review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as a therapeutic target. ToC blurb Inflammasome signaling in myeloid cells largely protects against microbial infections. Aberrant inflammasome signaling promotes chronic inflammation, which contributes to tumorigenesis. This Review presents an overview of the diverging roles of inflammasomes in cancer and discuss its targeting potential in anti-cancer therapy.

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Section: Metastasismentioning

confidence: 93%

“…■ Increased metastasis in mice injected with Aim2-silenced HCC cells 180 . ■ Decreased MC38 metastatic tumors in the liver of Nlrp3 −/− mice 64 . ■ Increased MC38 metastatic tumors in the livers of Casp1 −/− Casp11 −/− , Nlrp3 −/− , Il18 −/− and Il18r −/− mice 63 .…”

Section: Diverse Roles Of Inflammasomes Across Different Cancersmentioning

confidence: 99%

Diverging inflammasome signals in tumorigenesis and potential targeting

2019

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“…Clinicians have increasingly focused their attention on the association between inflammatory indexes and prognosis in patients with CRC. [25][26][27][28][29][30] Among these indexes, the SII is reportedly the most relevant biomarker for this purpose. The association between SII and prognosis in patients with CRC has been well studied.…”

Section: Discussionmentioning

confidence: 99%

<p>Creation of a Novel Inflammation-Based Score for Operable Colorectal Cancer Patients</p>

Huang¹,

Cao²,

Wang³

et al. 2020

JIR

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Aim: Systemic inflammation has been implicated in the progression of patients with colorectal cancer (CRC). We evaluated the prognostic ability of a comprehensive score based on several inflammatory indexes in operable CRC patients. Patients and Methods: Between July 2013 and September 2017, this study retrospectively identified 1279 CRC patients receiving radical surgery in Wuhan Union Hospital and randomly assigned them into training (N=921) and validation (N=358) sets. A novel score, the CRC-specific inflammatory index (CSII), was developed from a series of inflammatory indexes significantly associated with survival in patients with CRC. This novel score was then divided into three categories and compared to the well-known systematic inflammatory index (SII) and TNM stage. Finally, a survival nomogram was generated by combining the CSII and other informative clinical features. Results: The CSII-OS was calculated as 1.110×lg ALRI + 1.082×CAR + 0.792×PI, while CSII-DFS was 1.709×lg ALRI + 1.033×CAR based on multivariable Cox regression analysis. Patients with high CSII experienced a worse OS (HR=23.72, 95% CI, 11.30-49.78, P <0.001) and worse DFS (HR=15.62, 95% CI, 6.95-35.08, P <0.001) compared to those in CRC patients with low CSII. Moreover, ROC analyses showed that the CSII possessed excellent performance (AUC=0.859) in predicting OS and DFS. The AUC of the OS nomogram based on CSII, TNM stage, and chemotherapy was 0.897, while that of the DFS nomogram based on CSII, T stage, and TNM stage was 0.873. High-quality calibration curves in both OS and DFS nomograms were observed. Verification in the validation dataset showed results consistent with those in the training dataset. Conclusion: The CSII is a CRC-specific prognostic score based on the combination of available inflammatory indexes. High CSII is a strong predictor of worse survival outcomes. The CSII also exhibits better predictive performance compared to SII or TNM stage in operable CRC patients.

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“…The assembly of this complex can induce the maturation and secretion of pro-inflammatory factors, such as IL-1β and IL-18, thus promoting the development of an inflammatory response (14). Additionally, NLRP3 is associated with tumor development NLRP3 signaling activation in macrophages can contribute to colorectal cancer cell migration and invasion (15). NLRP3 inflammasomes serve a vital role in the regulation of the proliferation and migration of lung cancer A549 cells (16).…”

Section: Introductionmentioning

confidence: 99%

Ursolic acid inhibits the invasiveness of A498 cells via NLRP3 inflammasome activation

et al. 2020

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Renal cell cancer is a common malignant tumor of the urinary system. Ursolic acid (UA) serves an important antitumor role in certain types of cancer, such as lung cancer, breast cancer and hepatocellular carcinoma; however, to the best of our knowledge, the effect of UA on renal cancer has not yet been investigated. In the present study, A498 cells were treated with different concentrations of UA for 12, 24 and 48 h, and then MCC950, an inhibitor of the NLR family pyrin domain-containing 3 (NLRP3) receptor, was added to block NLRP3 signaling. The proliferation of A498 cells was analyzed using an MTS assay and invasiveness was analyzed using a Transwell assay. The expression levels of NLRP3, cleaved caspase-1, IL-1β and MMP-2 were detected using western blotting. The present results demonstrated that the invasiveness of A498 cells was significantly decreased following UA treatment (P<0.05), while expression levels of NLRP3, cleaved caspase-1 and IL-1β were significantly increased, and MMP-2 expression was decreased following UA stimulation (P<0.05). This was reversed by MCC950 treatment (P<0.05), with the exception of NLRP3. In conclusion, the present results indicated that UA exposure decreased the proliferation and invasiveness of A498 cells. Additionally, UA exposure significantly decreased MMP-2 production and induced the activation of NLRP3 inflammasome, which was reversed by MCC950 treatment, indicating that NLRP3 activation may be involved in UA inhibition of A498 cell invasiveness.

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NLRP3 inflammasomes in macrophages drive colorectal cancer metastasis to the liver

Cited by 80 publications

References 26 publications

Diverging inflammasome signals in tumorigenesis and potential targeting

Diverging inflammasome signals in tumorigenesis and potential targeting

<p>Creation of a Novel Inflammation-Based Score for Operable Colorectal Cancer Patients</p>

Ursolic acid inhibits the invasiveness of A498 cells via NLRP3 inflammasome activation

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