| First Author | Kamata T | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 12 | Pages | 107802 |
| PubMed ID | 32579928 | Mgi Jnum | J:292605 |
| Mgi Id | MGI:6445115 | Doi | 10.1016/j.celrep.2020.107802 |
| Citation | Kamata T, et al. (2020) Fibroblast-Derived STC-1 Modulates Tumor-Associated Macrophages and Lung Adenocarcinoma Development. Cell Rep 31(12):107802 |
| abstractText | The tumor microenvironment (TME) consists of different cell types, including tumor-associated macrophages (TAMs) and tumor-associated fibroblasts (TAFs). How these cells interact and contribute to lung carcinogenesis remains elusive. Using (G12D)KRAS- and (V600E)BRAF-driven mouse lung models, we identify the pleiotropic glycoprotein stanniocalcin-1 (STC1) as a regulator of TAM-TAF interactions. STC1 is secreted by TAFs and suppresses TAM differentiation, at least in part, by sequestering the binding of GRP94, an autocrine macrophage-differentiation-inducing factor, to its cognate scavenger receptors. The accumulation of mature TAMs in the Stc1-deficient lung leads to enhanced secretion of TGF-beta1 and, thus, TAF accumulation in the TME. Consistent with the mouse data, in human lung adenocarcinoma, STC1 expression is restricted to myofibroblasts, and a significant increase of naive macrophages is detected in STC1-high compared with STC1-low cases. This work increases our understanding of lung adenocarcinoma development and suggests new approaches for therapeutic targeting of the TME. |
