Abstract
Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The role of CD147 on cytokine production has been observed in inflammation-related diseases, but not in CCA. Therefore, this study was focused on CD147-promoting proinflammatory cytokine production and functions. Proinflammatory cytokine profiles were compared between CD147 expressing CCA cells and CD147 knockout cells (CD147 KO). Three cytokines, namely interleukin (IL)-6, IL-8, and granulocyte–monocyte colony-stimulating factor (GM-CSF), were dramatically diminished in CD147 KO clones. The involvement of the CD147-related cytokines in CCA invasion was established. CD147-promoted IL-6, IL-8, and GM-CSF secretions were regulated by NF-κB nuclear translocation, Akt activation, and p38 phosphorylation. CD147-fostering IL-6 production was dependent on soluble CD147, CD147 homophilic interaction, and NF-κB function. The overexpression of specific genes in CCA tissues compared to normal counterparts emphasized the clinical importance of these molecules. Altogether, CD147-potentiated proinflammatory cytokine production leading to CCA cell invasion is shown for the first time in the current study. This suggests that modulation of CD147-related inflammation might be a promising choice for advanced CCA treatment.
Highlights
Cholangiocarcinoma (CCA) is an aggressive cancer of bile ducts, which is highly prevalent in the Northeast of Thailand [1]
The results showed that DHMEQ effectively suppressed IL-6, IL-8, and granulocyte–monocyte colony-stimulating factor (GM-CSF) (Figure 7C,E)
The tight relationship between chronic inflammation and CCA progression suggests targeting chronic inflammation might be a novel target for CCA treatment, in advanced stages [4,5,6,7,8]
Summary
Cholangiocarcinoma (CCA) is an aggressive cancer of bile ducts, which is highly prevalent in the Northeast of Thailand [1]. It is a significant cancer-related health problem in the area. Proinflammatory cytokines potentiate chronic inflammation-related CCA pathogenesis, and progression is established [4,5,6,7,8]. This process is independent of CCA causative agents. Depletion of CD147-Alleviated Proinflammatory Cytokine Expressions in CCA CM.
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