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Journal of Cancer Research and Clinical Oncology

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11.06.2021 | Original Article – Cancer Research

Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection

verfasst von: Wei-wei Wang, Lipei Wu, Wenying Lu, Wei Chen, Wenhui Yan, Chunrun Qi, Shihai Xuan, Anquan Shang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2021

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Abstract

Background

Intra-abdominal infection after curative surgery for colorectal cancer is a serious complication associated with an increased risk of recurrence. Lipopolysaccharides (LPS)—an essential component of the cell wall of Gram-negative bacteria—were found to exert a protumorigenic effect by stimulating the inflammatory pathology and formation of neutrophil extracellular traps (NETs). This study was conducted to test whether LPS-induced formation of NETs promotes the development of cancer and metastasis.

Methods

The clinical characteristics, incidence of relapse, and serum myeloperoxidase–DNA complexes of 40 patients with infection and 40 patients without infection after curative surgery were analyzed. The effects of LPS on the induction of NETs were evaluated in a mouse model of colorectal cancer and liver metastasis. The toll-like receptor 9 (TLR9)—a DNA receptor—was knocked down to assess its effect on the mitogen-activated protein kinase pathway and activities implicated in the formation of NETs.

Results

Analysis of the clinical data obtained from these patients showed the significant relation of the formation of NETs and incidence of metastasis and survival rates. Subsequent in vitro experiments revealed an increased level of citrullinated-histone H3 and myeloperoxidase–DNA in LPS-injected mice with colorectal cancer. In the mimic metastatic model, injection of LPS enhanced the metastatic capacity, which was then attenuated by DNase I. This suggested that the formation of NETs was activated by LPS. Injection of TLR9-knockdown HCT116 cells in mice, followed by induction through LPS, mitigated the level of citrullinated-histone H3 and myeloperoxidase–DNA. This finding implied that the formation of NETs was suppressed.

Conclusion

These findings shed light on the mechanism underlying the relationship between the elevated rate of colorectal cancer recurrence in patients who underwent surgery and the incidence of infection. This mechanism involves the protumorigenic activities of LPS-induced formation of NETs. The NETs which could be mediated by the TLR9 and the mitogen-activated protein kinase signaling pathway.

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Titel: Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection
verfasst von: Wei-wei Wang
Lipei Wu
Wenying Lu
Wei Chen
Wenhui Yan
Chunrun Qi
Shihai Xuan
Anquan Shang
Publikationsdatum: 11.06.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-021-03682-8

Springer Medizin

Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection