Osteosarcoma (OS) is the most common malignant bone tumor, with a high incidence in children and adolescents. Frequent tumor metastasis and high postoperative recurrence rates are the most common challenges of OS. However, the detailed mechanisms are unclear. Here, researchers found that CD248 is highly expressed in OS tissues and correlated with lung metastasis of OS. Knockdown of CD248 in OS cells significantly inhibited cell migration, invasion, and metastasis, but had no significant effect on cell proliferation. Knockdown of CD248 significantly suppressed lung metastasis in nude mice. Mechanistically, CD248 promotes the interaction between ITGB1 and the extracellular matrix (ECM) proteins CYR61 and FN, thereby activating the FAK-paxillin pathway and promoting focal adhesion formation and metastasis in OS. These data suggest that CD248 may promote tumor migration and metastasis by enhancing the interaction between ITGB1 and certain ECM proteins. Therefore, CD248 is a potential marker for diagnosis and an effective target for the treatment of metastatic OS.
Here, the researchers explored whether CD248 could regulate the migration and invasion of OS cells. The results of the wound repair assay and Transwell assay showed that the migration ability of CD248-knockdown SJSA-1 and HOS cells was significantly reduced compared with the control group (Figure 1A-D). Similarly, the results of transwell with Matrigel also showed that the invasion ability of CD248-knockdown SJSA-1 and HOS cells was inhibited (Figure 1E-F). The researchers also used CD248-overexpressing MG63 cells (which originally had very low CD248 expression) to verify the role of CD248 in cell migration. The results of the Transwell assay showed that CD248 overexpression significantly enhanced the migration ability of MG63 cells. These results confirmed that CD248 can significantly promote the migration and invasion of OS cells in vitro.
Figure 1. Knockdown of CD248 inhibited migration and invasion of OS cells in vitro. (Lu S, et al., 2023)