| First Author | Zhang Y | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 7 | Pages | 1586-1598 |
| PubMed ID | 28202524 | Mgi Jnum | J:242083 |
| Mgi Id | MGI:5904396 | Doi | 10.1158/0008-5472.CAN-16-1569 |
| Citation | Zhang Y, et al. (2017) Scavenger Receptor A1 Prevents Metastasis of Non-Small Cell Lung Cancer via Suppression of Macrophage Serum Amyloid A1. Cancer Res 77(7):1586-1598 |
| abstractText | Mechanisms of cross-talk between tumor cells and tumor-associated macrophages (TAM), which drive metastasis, are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics, and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced stage NSCLC patients in the Harvard Lung Cancer Study cohort. Two SNPs (rs17484273, rs1484751) in SR-A1 were associated significantly with poor overall survival in this cohort. Data from The Cancer Genome Atlas showed considerable downregulation of SR-A1 in lung tumor tissues. The association of SR-A1 with prognosis was validated in animal models in the context of lung cancer metastasis. Macrophages derived from mice genetically deficient for SR-A1 exhibited accelerated metastasis in a model of lung cancer. On the other hand, tumor cell seeding, migration, and invasion, as well as macrophage accumulation in lung cancer tissue, were enhanced in SR-A1-deficient mice. SR-A1 deletion upregulated serum amyloid A1 (SAA1) in macrophages via MAPK/IkappaB/NFkappaB signaling. SAA1 promoted tumor cell invasion and macrophage migration in vitro and in vivo, but these effects were blocked by administration of an anti-SAA1 antibody. Overall, our findings show how SR-A1 suppresses lung cancer metastasis by downregulating SAA1 production in TAMs. Cancer Res; 77(7); 1586-98. (c)2017 AACR. |
