Panoply™ Human CCR4 Over-expressing Stable Cell Line

Research suggests that chemokine receptors contribute to poor prognosis in patients with hepatocellular carcinoma (HCC). Here, researchers demonstrate for the first time that CCR4 is overexpressed in HCC tissues and that elevated CCR4 expression in HCC tissues is positively correlated with tumor capsule breach and vascular invasion. Although CCR4 overexpression had no significant effect on HCC cell proliferation in vitro, it significantly promoted HCC cell growth in vivo. The underlying mechanism may involve angiogenesis. Interestingly, unlike its effect on proliferation, CCR4 overexpression not only promotes HCC metastasis in vitro and in vivo but also induces epithelial-mesenchymal transition (EMT) in HCC cells. Subsequently, researchers identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4, demonstrating its crucial role in CCR4-mediated HCC cell invasion, with the ERK/AKT signaling pathway upregulating MMP2 expression. A positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. Taken together, these studies suggest that the chemokine receptor CCR4 promotes HCC malignancy and promotes HCC cell metastasis through the ERK/AKT/MMP2 pathway. CCR4 may serve as a potential new diagnostic and prognostic marker for HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.

Chemokines have been shown to be associated with cancer metastasis and tumor angiogenesis, acting through activation of several signaling pathways, including extracellular-regulated protein kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). Here, researchers have demonstrated that CCR4 promotes HCC metastasis and angiogenesis in vitro and in vivo. Therefore, they sought to elucidate the potential signaling mechanisms underlying CCR4-mediated MMP2 upregulation. Compared with controls, CCR4-overexpressing HepG2 cells showed increased ERK phosphorylation, AKT phosphorylation, and P38 phosphorylation (Figure 1C, D). The opposite pattern was observed in the CCR4-silencing group (Figure 1A, B). Together, these findings suggest that, in HCC, CCR4 upregulates MMP2 through the ERK/AKT pathway, thereby promoting cancer metastasis and tumor angiogenesis (Figure 1E, F).

Figure 1. CCR4 up-regulates MMP2 expression through ERK/MAPK/AKT signaling pathway. (Cheng X, et al., 2017)