RRC ID 71644
Author Takeba Y, Ohta Y, Ootaki M, Kobayashi T, Kida K, Watanabe M, Koizumi S, Otsubo T, Iiri T, Matsumoto N.
Title Identification of interleukin-16 production on tumor aggravation in hepatocellular carcinoma by a proteomics approach.
Journal Tumour Biol
Abstract BACKGROUND:Cytokines play an important role in the immune response, angiogenesis, cell growth, and differentiation in hepatocellular carcinoma (HCC).
OBJECTIVE:We performed a comprehensive study to identify tumor-related cytokines and pathways involved in HCC pathogenesis.
METHODS:Cytokine production was evaluated in human HCC tissues and adjacent non-tumor tissues using an antibody-based protein array technique. We compared cytokine expression in HCC tissues with that of hepatic hemangioma (HH), liver metastasis of colorectal cancer, and noncancerous liver tissues from transplantation donors. The protein levels and localization of the candidate cytokines were analyzed by western blotting and immunohistochemistry.
RESULTS:Increased expression of interleukin (IL)-1 receptor antagonist, macrophage migration inhibitory factor, and IL-16 was observed in HCC and paired adjacent non-tumor tissues compared with noncancerous livers. In addition, there were increased IL-16 levels in HCC tissues compared with HH. IL-16 treatment significantly increased cell proliferation in vitro. The expression of extracellular signal-regulated kinase (ERK)1/2 and cyclin D1 was markedly increased in cells from two HCC cell lines, Huh7 and HepG2, in a dose- and time-dependent manner. Phosphorylated to total ERK1/2 ratio was increased in Huh7 cells following IL-16 50 ng/ml, but not HepG2 cells. ERK phosphorylation have occurred earlier than protein accumulation at 48 h. Pretreatment with the ERK inhibitor, FR18024, or an anti-IL-16 antibody reduced the increase in IL-16 production in HCC cells.
CONCLUSIONS:These results suggest that cell proliferation induced by IL-16 is mediated through the ERK pathway, thus, we identified a new factor associated with HCC tumor growth.
Volume 43(1)
Pages 309-325
Published 2021-1-1
DOI 10.3233/TUB-211507
PII TUB211507
PMID 34897107
MeSH Carcinoma, Hepatocellular / drug therapy Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Cell Proliferation / drug effects Colorectal Neoplasms / drug therapy Colorectal Neoplasms / genetics Colorectal Neoplasms / pathology Gene Expression Regulation, Neoplastic Hemangioma / drug therapy Hemangioma / genetics Hemangioma / pathology Hep G2 Cells Humans Interleukin 1 Receptor Antagonist Protein / genetics* Interleukin-16 / antagonists & inhibitors Interleukin-16 / biosynthesis Interleukin-16 / genetics* Interleukin-16 / pharmacology Liver / drug effects* Liver / metabolism Liver / pathology Liver Neoplasms / drug therapy Liver Neoplasms / genetics* Liver Neoplasms / pathology MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / genetics Macrophage Migration-Inhibitory Factors / genetics Neoplasm Metastasis Proteomics
IF 3.65
Human and Animal Cells HuH-7 Hep G2(RCB1648)