Panoply™ Human CCL20 Knockdown Stable Cell Line

Chemotherapy resistance in triple-negative breast cancer (TNBC) poses a significant challenge to improving patient survival rates. Currently, the mechanisms underlying resistance to taxane-based chemotherapy in TNBC remain insufficiently understood. Here, researchers demonstrate that levels of C-C motif chemokine ligand 20 (CCL20) are significantly elevated in breast cancer patients who fail to achieve pathological complete response during taxane-based chemotherapy. Furthermore, CCL20 promotes the self-renewal and maintenance of breast cancer stem cells (BCSCs)-or breast cancer stem-like cells-via the activation of the p65 NF-κB pathway (mediated by PKCζ or p38 MAPK), thereby significantly increasing the BCSC population and enhancing their resistance to taxanes. Further investigation revealed that CCL20-induced NF-κB activation upregulates the expression of ATP-binding cassette subfamily B member 1 (ABCB1, also known as multidrug resistance protein 1/MDR1), leading to the efflux of taxanes from the cell. These findings indicate that chemotherapy-induced CCL20 mediates chemoresistance through the upregulation of ABCB1. Concurrently, NF-κB activation promotes CCL20 expression, establishing a positive feedback loop between the NF-κB and CCL20 pathways that provides a sustained driving force for chemoresistance in breast cancer cells.

To determine whether CCL20 regulates the malignancy of breast cancer, researchers first analyzed the Cancer Genome Atlas (TCGA) database and found that CCL20 was highly expressed in triple-negative breast cancer (TNBC) compared to non-triple-negative breast cancer (non-TNBC) (Figure 1A); the same expression pattern was observed at both mRNA and protein levels in breast cancer cell lines (Figure 1B and 3C). These findings indicate that CCL20 expression is positively correlated with breast cancer malignancy. To investigate the function of CCL20 in TNBC, researchers knocked down CCL20 in TNBC cell lines and found that this significantly inhibited cancer cell proliferation (Figure 1D). In CCL20-knockdown MDA-MB-231 cells, cell invasion capability through Matrigel (Figure 1E and F) and anchorage-independent growth capability (Figure 1G) were also reduced. Furthermore, researchers generated cell lines overexpressing two CCL20 isoforms (CCL20v1 and CCL20v2). The results showed that CCL20 overexpression significantly promoted the proliferation (Figure 1H), invasion capability (Figure 1I and J), and anchorage-independent growth capability (Figure 1K) of MDA-MB-231 and SUM159 cells.

Figure 1. CCL20 promoted tumor progression and enhanced the chemoresistance to taxanes in TNBC. (Chen W, et al., 2018)