Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis.
Cell
; 2024 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-39378878
ABSTRACT
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)-ß2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-ßRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-ß2 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-ß2 receptor. Restoring TGF-ßRIII in aggressive cells reinstates TGF-ß2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-ß2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos