Neutrophils promote hepatic metastasis growth through fibroblast growth factor 2–dependent angiogenesis in mice

Gordon-Weeks, Alex; Lim, Su Yin; Yuzhalin, Arseniy E.; Jones, Keaton; Markelc, Boštjan; Kim, K. Jin; Buzzelli, Jon N.; Fokas, Emmanouil; Cao, Yuze; Smart, Sean; Muschel, Ruth J.

doi:10.1002/hep.29088

Cited by 114 publications

(97 citation statements)

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“…Therefore, the role of TANs in tumors remains controversial, including CRC 18, 19, 22. Many studies have found neutrophils to be an independent factor of poor prognosis and promote the growth of distance metastases in CRC 23, 24. However, other studies have revealed that tumor‐infiltrating neutrophils are associated with a better prognosis in CRC and might promote antitumor immunity 22, 25.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

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Interleukin (IL)‐37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL‐37 expression and neutrophil levels in CRC. We retrospectively analyzed IL‐37 expression, CD66b+ neutrophil levels, and mismatch repair (MMR) status in 337 paraffin‐embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan‐Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL‐37 expression and high CD66b+ neutrophil levels were significantly associated with diminished disease‐free survival (DFS) and overall survival (OS), and patients with MMR‐deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL‐37, CD66b+ neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C‐index: training cohort, 0.798 (95% confidence interval:0.764‐0.832) and 0.828 (0.796‐0.860), respectively; validation cohort, 0.739 (0.696‐0.783) and 0.761 (0.715‐0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL‐37, CD66b+ neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

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“…T" [19]. "Metastasis-associated neutrophils expressed substantially more ibroblast growth factor 2 (FGF2) than naïve neutrophils, indicating neutrophil polarization by the tumor microenvironment" [22]. "In control animals changes to the hepatic microenvironment associated with obesity sustained the presence of tumor cells in the liver and increased the incidence of hepatic metastases after intrasplenic/portal inoculation of colon carcinoma cells" [23].…”

Section: Discussionmentioning

confidence: 99%

“…Here, we show, using FGF2 as an example, that identi ication of factors responsible for the protumoral effects of in iltrating myeloid cells can be used to target established liver metastases. Such therapies could be utilized to limit disease progression and potentiate the effects of standard ablative therapies" [22].…”

Section: Fusion Hybrid Hypothesis Of Cancer Cell Metastasis Metastatmentioning

confidence: 99%

Similarity between Some Biological Systems, Organotropism and Metastatic Process: Active Role Played By Secondary Organ?

Luisetto¹

2018

Insights Biol Med

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According to literature, about 90% of death from cancer is related to metastasis. Metastatic process present many similarity to some other biological processes. Once we have examined some relevant biomedical literature, by understanding the real causes of metastasis, it would become much more possible to introduce new therapeutic strategies to delay or in some cases even to stop this kind of killer process. Breast cancer, as an example, produces metastasis to different organs, which seems to be related to the subtype. We believe that a deep understanding of the roles of breast cancer cells and their interactions with the liver microenvironment in early breast cancer metastasis could be a crucial factor for the design and development of effective BCLM breast cancer liver metastases therapeutic strategies and to better understand the general process. Let's suppose the secondary organ or organs can be considered as incubator/s for the primary metastatic cells. What kind of consequences we can have in therapy fi eld if there is an active regulating role in determining the location of secondary cancers?Let's observe the role played by liver, bone marrow, CNS central nervous system, lungs, lymphocytes and other secondary locations/organs a little bit closer or maybe from a different angle let's suppose we try to come up with just a hypothesis. Just let's take this as a possibility, and we take the thread to see where it takes us.

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“…In other contexts, infiltrating neutrophils function to promote cancer progression and metastasis . With respect to liver metastases, neutrophils promote the formation and growth of hepatic metastases from multiple solid cancers …”

mentioning

confidence: 99%

“…Neutrophils positively impact the metastatic process through a variety of functions, including their ability to enhance cancer cell entrapment/seeding within neutrophil extracellular traps, promote cancer cell extravasation, and stimulate angiogenesis . In the context of tumor angiogenesis, there are several mechanisms through which neutrophils play a proangiogenic role.…”

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confidence: 99%

Expanding the armamentarium for neutrophil‐mediated angiogenesis

Hsu

Siegel

2017

Hepatology

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Neutrophils promote hepatic metastasis growth through fibroblast growth factor 2–dependent angiogenesis in mice

Cited by 114 publications

References 50 publications

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Similarity between Some Biological Systems, Organotropism and Metastatic Process: Active Role Played By Secondary Organ?

Expanding the armamentarium for neutrophil‐mediated angiogenesis

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