Panoply™ Human CXCL10 Over-expressing Stable Cell Line

Metastasis induced by chronic inflammation has long been recognized as a major obstacle in cancer treatment. Tumor necrosis factor-alpha (TNF-α) is a key inflammatory mediator within the tumor microenvironment; it influences tumor progression by inducing a complex network of chemokines. Recent studies indicate that the CXCL10/CXCR3 axis affects cancer cell invasion and metastasis, while epithelial-mesenchymal transition (EMT) is a primary driver of rapid proliferation and distant organ metastasis in colon cancer (CC) cells. However, it remains unclear whether TNF-α-induced chronic inflammation synergistically enhances EMT-mediated colon cancer metastasis by promoting chemokine expression. Here, researchers found that TNF-α activates two parallel signaling pathways-PI3K/Akt and p38 MAPK-thereby stimulating the nuclear translocation of the p65 subunit of the downstream NF-κB pathway to initiate CXCL10 transcription. CXCL10 enhances the metastatic potential of colon cancer cells by activating small GTPases such as RhoA and Cdc42. Furthermore, CXCL10 overexpression significantly boosts the tumorigenicity and migratory capacity of colon cancer cells in vivo. Further investigation revealed that CXCL10 activates the PI3K/Akt pathway via the CXCR3 receptor and inhibits GSK-3β phosphorylation, leading to the upregulation of Snail and thereby regulating the EMT process in colon cancer cells.

In this study, researchers established SW480 and SW620 cell lines stably overexpressing CXCL10 (SW480-CXCL10 and SW620-CXCL10) alongside their corresponding control cell lines (SW480-Vector and SW620-Vector). These engineered cell lines, as well as wild-type SW480 and SW620 cells, were subcutaneously inoculated into nude mice to evaluate their tumorigenic potential. As shown in Figure 1A, the proliferation rate of CXCL10-overexpressing colorectal cancer (CC) cells in vivo was significantly higher than that of the corresponding control groups. Unsurprisingly, Ki-67 expression levels were significantly elevated in tumors derived from CXCL10-overexpressing CC cells compared to those formed by control and wild-type CC cells (Figure 1B). Furthermore, the researchers injected the aforementioned CC cells via the tail vein to observe the formation of pulmonary metastases. The results demonstrated that SW480-CXCL10 and SW620-CXCL10 cells formed a greater number of metastatic foci in the lungs of nude mice compared to the corresponding control and wild-type CC cells, indicating that the upregulation of CXCL10 expression increased the incidence of pulmonary metastasis (Figure 1C). In summary, activation of the CXCL10/CXCR3 pathway enhances the metastatic capability of CC cells in vivo; CXCL10 expression significantly boosts the tumorigenicity and motility of CC cells, while promoting their growth in vivo and migration to distant organs.

Figure 1. CXCL10 increases tumor growth and CC cell metastasis in vivo. (Wang Z, et al., 2021)