The inhibition of HIF-1 alpha activity in tumors from YC-1-treated mice is associated with blocked angiogenesis and an inhibition of tumor growth. YC-1 has the potential to become the first antiangiogenic anticancer agent to target HIF-1 alpha.

Objective: Integrin-associated protein (CD47) binds specifically to the inhibitory receptor signal-regulatory protein. This study was designed to evaluate the role of CD47 in natural killer (NK) cell-mediated cytotoxicity against cancer cells. Methods: Head-and-neck squamous cell carcinoma (HNSCC) cell lines were analyzed for the expression of CD47 and susceptibility to NK cell-mediated killing. Cytolytic activity was assessed by ⁵¹Cr-specific release assays and by measuring cytokine production. Results: HNSCC cell lines that had high CD47 expression showed lower levels of NK cytotoxicity than those with low CD47 expression. After pre-treating cells with neutralizing major histocompatibility complex (MHC) class I or anti-CD47 antibodies, NK cell-mediated cytotoxicity against HNSCC cell lines increased. In addition, when CD47 cDNA was transfected into Caco-2 cells, NK cell-mediated cytotoxicity decreased. Conclusion: These findings suggest that CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer.