Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-γ production by tumor-associated macrophages

Abstract

Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A-/-) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A-/- mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-γ mRNA increased significantly in tumor tissues from SR-A-/- mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-γ production by cultured macrophages, and production of NO and IFN-γ increased in SR-A-/- macrophages in vitro. IFN-β production by cultured macrophages was also elevated in SR-A-/- macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A-/- mice because of upregulation of NO and IFN-γ production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4-IFN-β signaling. (Cancer Sci 2009). © 2009 Japanese Cancer Association.