Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma

Abstract

Background: Our previous work demonstrated upregulated CD47 in Oral Squamous Cell Carcinoma (OSCC).

Objective: In the present study, we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms.

Methods: The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified.

Results: Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in the apoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knockeddown Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitro phagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling.

Conclusion: In summary, the knockdown of CD47 downregulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.

Keywords: CD47; Cell proliferation; STAT3/JAK2 signaling; macrophage; tumor development; xenograft transplantations.