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Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

ABSTRACT: The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

SUBMITTER: Rayes RF

PROVIDER: S-EPMC5884657 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

Rayes Roni F RF Milette Simon S Fernandez Maria Celia MC Ham Boram B Wang Ni N Bourdeau France F Perrino Stephanie S Yakar Shoshana S Brodt Pnina P

Oncotarget 20180228 21

The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prio ...[more]

PMID: 29644002

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Project description:Purpose Hepatic metastasis of colon carcinoma seriously affects the prognosis of patients, and miRNA has attracted much attention in predicting hepatic metastasis of colon carcinoma (CC). This research aimed to explore the predictive role of miR-210 in serum for recurrence and prognosis of CC patients with hepatic metastasis. Methods Altogether, 150 patients with liver metastases of CC (research group, RG) and 130 patients with non-metastatic of CC (control group, CG) admitted to People’s Hospital of Deyang City from March 2012 to March 2015 were obtained and their serum was collected. miR-210 in the RG and the CG, and miR-210 in the RG after radiofrequency ablation treatment were detected, the relationship between miR-210 and pathological parameters of CC patients with hepatic metastasis was analyzed, and patients in the RG were followed up for 5 years to analyze the recurrence, overall survival (OS) and disease-free survival (DFS). The area under the curve (AUC) of receiver operating characteristic curve (ROC) was applied to test the predictive value of miR-210. Cox regression was applied to analyze the independent prognostic factors of patients. Results miR-210 in the RG was evidently higher than that in the CG, and AUC for distinguishing hepatic metastasis of CC was 0.907. miR-210 had a close correlation with lymph node metastasis, distant metastasis and pathological differentiation. After treatment, miR-210 in the RG was evidently reduced, and the serum was higher in patients with recurrence and with poor prognosis. AUC for predicting recurrence was 0.858, and AUC for predicting poor prognosis was 0.843. High miR-210 was closely related to lower 5-year OS and DFS and is also an independent prognostic factor affecting patients’ 5-year OS. Conclusion miR-210 is enhanced in hepatic metastasis of CC, which is a serological biomarker for predicting recurrence and prognosis of patients with hepatic metastasis of CC after radiofrequency ablation, and has great clinical application value.

Dataset Information

Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

Publications

Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

Similar Datasets

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