Asset Details
Do you wish to reserve the book?
Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation
Do you wish to request the book?
Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation
2017
Overview
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis. In an orthotopic mouse model of HCC,
Rarres2
−/−
mice exhibited aggressive tumor growth and lung metastasis, whereas chemerin overexpression greatly inhibited tumor growth. The tumor-inhibitory effect of chemerin was accompanied by a shift in tumor-infiltrating immune cells from myeloid-derived suppressive cells (MDSCs) to interferon-γ
+
T cells and decreased tumor angiogenesis. Furthermore, we demonstrated that the tumor-inhibitory effect of chemerin was partly dependent on T cells, as chemerin overexpression could inhibit tumor growth, albeit to a lesser extent, in
Rag1
−/−
mice when compared with wild-type controls. Mechanistically, chemerin inhibited nuclear factor-κB activation and the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-6) by tumor cells and tumor-associated endothelial cell, respectively, via its receptors, and consequently, MDSC induction was impaired, leading to restoration of antitumor T-cell response and decreased tumor angiogenesis. Clinically, systemic and tumor levels of chemerin were found to inversely correlate with circulating concentrations of GM-CSF or IL-6 and tumor-infiltrating myeloid cells, respectively, in HCC patients. Moreover, neutralization of GM-CSF and IL-6 abrogated HCC progression and MDSC accumulation in
Rarres2
−/−
mice. In conclusion, our study reveals the tumor-inhibitory effect of chemerin by suppressing inflammatory tumor microenvironment with therapeutic implications for inflammation-associated cancer-like HCC.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/21
/ 13/31
/ 13/51
/ 13/89
/ 38/23
/ 38/77
/ 45/44
/ 64/60
/ Animals
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - pathology
/ Female
/ Gene Expression Regulation, Neoplastic
/ Granulocyte-macrophage colony-stimulating factor
/ Granulocyte-Macrophage Colony-Stimulating Factor - genetics
/ Granulocyte-Macrophage Colony-Stimulating Factor - immunology
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - immunology
/ Humans
/ Intercellular Signaling Peptides and Proteins - genetics
/ Intercellular Signaling Peptides and Proteins - immunology
/ Liver Neoplasms, Experimental - genetics
/ Liver Neoplasms, Experimental - immunology
/ Liver Neoplasms, Experimental - pathology
/ Lungs
/ Male
/ Medicine
/ Mice
/ Neoplasm Proteins - genetics
/ Neoplasm Proteins - immunology
/ Oncology
/ Rodents
