CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.
Elife
; 82019 04 16.
Article
in En
| MEDLINE
| ID: mdl-30990165
ABSTRACT
Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Chemokine CCL5
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Elife
Year:
2019
Type:
Article
Affiliation country:
United States