| First Author | Dalla E | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 23 | Pages | 6631-6648.e20 |
| PubMed ID | 39378878 | Mgi Jnum | J:358052 |
| Mgi Id | MGI:7779277 | Doi | 10.1016/j.cell.2024.09.016 |
| Citation | Dalla E, et al. (2024) Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis. Cell |
| abstractText | Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-beta2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-betaRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-beta2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-beta2 receptor. Restoring TGF-betaRIII in aggressive cells reinstates TGF-beta2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-beta2 signaling allows cancer cells to overcome macrophage-mediated growth suppression. |
