Fig. 8

Schematic diagram of VNP-shCCDC25 blocking CCDC25-NET-DNA and remodeling immunity in B16F10-bearing mice and 4T1-bearing mice. Overall, VNP-shCCDC25 inhibits tumor lung metastasis after intravenous injection in mice. Specifically, VNP-shCCDC25 mediates tumor lung metastasis inhibition through the following 3 mechanisms. (1) VNP-shCCDC25 knocked down CCDC25 and its downstream prometastasis signaling pathway ILK-Parvb-RAC1-CDC42 after successful invasion of tumor cells, which in turn reduced the invasiveness of tumor cells. (2) The NETosis at tumor site was somewhat inhibited after knocking down CCDC25. (3) In TME, elevated infiltration rates of M1-Mφs and N1-NEs with antitumor phenotypes as well as effective activation of DCs were observed, suggesting that VNP-shCCDC25 can remodel TME and ultimately achieve tumor metastasis suppression