Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various cancers. However, the expression and function of GPNMB in patients with renal cell carcinoma (RCC) and BM remain unclear. Here, researchers investigated the clinical significance and biological function of GPNMB in RCC with BM. Results showed that high GPNMB expression levels were significantly correlated with the number and extent of BM, Fuhrman grade, and ERK expression in the primary tumor. Furthermore, GPNMB overexpression was significantly associated with poor prognosis (overall survival). Furthermore, researchers generated a GPNMB knockdown ACHN cell line. Low GPNMB expression inhibited RCC cell proliferation, as measured using the Cell Counting Kit-8 assay. Compared to cells transduced with negative control shRNA, GPNMB knockdown of renal cell carcinoma cells exhibited significantly reduced cell migration and invasion. Furthermore, phosphorylated ERK protein expression was lower in GPNMB knockdown ACHN cells compared to control cells. These results suggest that GPNMB plays an important role in tumor progression in renal cell carcinoma with bone marrow metastasis. It can serve as a predictive marker for bone marrow metastasis and a poor prognostic factor for renal cell carcinoma with bone marrow metastasis. GPNMB downregulation inhibits the proliferation, migration, and invasion of renal cell carcinoma, possibly by inhibiting the ERK signaling pathway.
Here, researchers investigated the effects of GPNMB knockdown on RCC cell proliferation. Western blot analysis showed that GPNMB protein expression levels were suppressed after shRNA transduction (Figure 1A). CCK-8 assays revealed that the cell proliferation capacity of GPNMB knockdown cells was significantly reduced compared with the NC group (Figure 1B). To investigate the invasion and migration capacity of GPNMB knockdown RCC cells, Transwell and Matrigel assays were performed (Figure 1C). Transwell assay results showed that the migration capacity of the GPNMB knockdown ACHN cell line was significantly inhibited compared with the control cells (Figure 1D). In addition, Matrigel assay results showed that the number of invasive cells in the GPNMB knockdown ACHN cell line was significantly lower than that in the control group (Figure 1D).
Figure 1. Effect of GPNMB downregulation. (Zhai J P, et al., 2022)