Here, researchers aimed to investigate the expression of CD74 and its potential role in human urothelial bladder carcinoma (UCB) in vitro and in vivo. The study showed that most muscle-invasive bladder cancer (MIBC) samples and only one high-grade UCB cell line, HT-1376, expressed CD74 compared with normal non-muscle-invasive bladder cancer (NMIBC) samples and other cell lines. CD74 knockdown HT-1376 cells showed reduced proliferation and invasion levels, and Western blotting assays showed that different treatments in vitro affected the levels of proteins related to proliferation, apoptosis, and invasion in the cells accordingly. Tumor formation and MVD assays showed that knockdown HT-1376 cells had less proliferation and angiogenesis compared with scrambled cells. Notably, J82 cells without CD74 signals in vitro presented CD74 expression in vivo. These studies reveal the potential role of CD74 in the proliferation, invasion, and angiogenesis of MIBC and may serve as a potential therapeutic target for UCB, but further studies are needed.
Compared with the scramble group, the proliferation ability of HT-1376 cells was weakened after CD74 knockdown (Figure 1A). Flow cytometry showed that compared with the scramble shRNA group, the proportion of cells in the G1 phase increased significantly after CD74 knockdown, and the proportion of cells in the G2 and S phases decreased significantly (Figure 1B). Cell invasion assay showed that the invasion ability of HT-1376 cells was significantly weakened after knocking down CD74 (Figure 1C, D). The results showed that the secretion of VEGF and MMP-9 was significantly reduced in CD74-knockdown-HT-1376 cells compared with the shRNA control, while not significantly reduced in MMP-2 (Figure 1E, F).
Figure 1. In vitro analysis of the effects of CD74-knockdown cells. (Gai J W, et al., 2018)