Class A1 Scavenger Receptor Deficiency Exacerbates Lung Cancer Metastasis By Promoting The Macrophage Recruitment And SAA1 Synthesis In Tumor Microenvironment In Mice

Macrophages in tumor microenvironment play a prominent role in tumor progression and metastasis.Class A1 scavenger receptor(SR-A1)represents an important player in macrophages by regulating apoptosis,polarization and cytokines synthesis of macrophages.However,the role of SR-A1 in lung cancer development is less elucidated.Our current study showed that Lewis lung carcinoma cells metastasized much faster in SR-A1 knockout mice along with an enhancement of macrophage accumulation in metastases,compared to that in wild-type mice.Bone marrow transplantation study showed that bone marrow SR-A1 deficiency could replicate the above metastasis-promoting phenotype.In vitro study we demonstrated that tumor-infiltrating SR-A1 KO macrophages showed greater migration ability and expressed higher level of serum amyloid A 1(SAA1),a kind of acute phase protein.Furthermore,we found that the increased SAA1 upregulated MCP-1 expression in macrophages,contributing to the enhanced recruitment of macrophages to the metastases.Moreover,SAA1 was proved to promote migration and invasion abilities for Lewis lung carcinoma cells.In addition,we found that the increased SAA1 was synthesized through MAPK/NF-(42)B pathway in SR-A1 null macrophages.Taken together,our study,for the first time,demonstrated that SR-A1 deficiency promoted lung cancer metastasis through enhancing the recruitment of macrophages to metastases microenvironment and promoting the migration and invasion of the Lewis lung carcinoma cells that was mediated by SAA1 produced by the recruited macrophages.Thus,upregulating SR-A1 expression in macrophages may be developed as a therapeutic approach to Non-small cell lung carcinoma metastasis.