Multiple studies have shown that transferrin receptor (TFRC) is highly expressed in various tumors and has been recognized as a cancer biomarker. However, its role in osteosarcoma (OS) has been rarely studied. Here, researchers explored the role and mechanism of TFRC in osteosarcoma cell proliferation, invasion, and migration. Studies have shown that TFRC is highly expressed in osteosarcoma, and its high expression is associated with poor prognosis in osteosarcoma patients. Knockdown of TFRC significantly reduced the proliferation, migration, and invasion of osteosarcoma cells, and in nude mouse xenograft experiments, TFRC knockdown effectively inhibited osteosarcoma cell growth. TFRC knockdown led to a decrease in intracellular total iron content and a significant decrease in RRM2 protein expression. Adding FAC or plasmids overexpressing RRM2 reversed the reduction in osteosarcoma cell proliferation, migration, and invasion caused by TFRC knockdown. Therefore, osteosarcoma cells regulate proliferation, migration, and invasion through TFRC overexpression; TFRC overexpression increases iron transport into cells and enhances RRM2 expression and activity.
TFRC is abnormally highly expressed in human osteosarcoma cells. Therefore, to investigate the role of TFRC in osteosarcoma, researchers constructed stable TFRC knockdown cell lines using the 143B and U2OS cell lines, which have relatively high TFRC expression (Figure 1A and B). Subsequently, they performed CCK-8 and colony formation assays to investigate the effect of TFRC knockdown on osteosarcoma cell proliferation. As shown in Figure 1C, the absorbance value of TFRC knockdown cells was significantly lower than that of the control group. Furthermore, the number of colonies formed in TFRC knockdown cells was also significantly lower than that in control cells (Figure 1D). These results indicate that TFRC knockdown can attenuate osteosarcoma cell proliferation. Researchers assessed cell migration ability using scratch assays and Transwell migration assays. The results showed that cell migration ability was significantly reduced after TFRC knockdown compared to the control group (Figures 1E and F). In addition, researchers used Matrigel Transwell invasion assays to assess the invasive ability of human osteosarcoma cells. The number of invasive cells in the experimental group was also significantly lower than that in the control group (Figure 1G). In summary, these results indicate that knocking down TFRC can inhibit the proliferation, migration, and invasion of human osteosarcoma cells.
Figure 1. TFRC knockdown inhibits the proliferation, migration, and invasion of human OS cells. (Ren G, et al., 2025)