The Role Of Class A Scavenger Receptor In Lung Cancer And Its Mechanism

Background:Lung cancer is the leading cause of cancer-related deaths around the world. In China, the morbidity and mortality of lung cancer have increased rapidly in recent decades. Class A scavenger receptor (SR-A) is a transmembrane receptor expressed mainly in macrophages. Macrophage scavenger receptor (MSR1) gene is located at8p22, a hot spot that houses many cancer related genes. The relationship between SR-A and lung cancer has not been elucidated. Nor is it clear how SR-A may contribute to lung carcinogenesis.Methods:SR-A null mice were used to investigate its role in lung cancer development.6-8week old female mice deficient in SR-A (SR-A-/-) and their littermate controls (WT) were injected subcutaneously (s.c.) with LLC cells into the flank. By using a bone marrow transfer (BMT) technique, we found that bone marrow derived cells (BMDC) from SR-A-/-mice transplanted into WT mice significantly sped up tumor growth and angiogenesis compared with mice that received WT BMDC.Results:Depletion of SR-A boosted the growth and angiogenesis of implanted Lewis lung carcinoma cells in mice. Cancer suppressing capability was attributable to macrophage specific SR-A as evidenced by bone marrow transfer assay. Conclusions: Our data provide strong evidence that loss of SR-A promotes lung cancer development. As such, fine-tuning SR-A activity may yield promising therapeutic solutions against lung cancer in the future.