Bidirectional activation of stem-like programs between metastatic cancer and alveolar type 2 cells within the niche.
Dev Cell
; 59(18): 2398-2413.e8, 2024 Sep 23.
Article
in En
| MEDLINE
| ID: mdl-38866011
ABSTRACT
A key step for metastatic outgrowth involves the generation of a deeply altered microenvironment (niche) that supports the malignant behavior of cancer cells. The complexity of the metastatic niche has posed a significant challenge in elucidating the underlying programs driving its origin. Here, by focusing on early stages of breast cancer metastasis to the lung in mice, we describe a cancer-dependent chromatin remodeling and activation of developmental programs in alveolar type 2 (AT2) cells within the niche. We show that metastatic cells can prime AT2 cells into a reprogrammed multilineage state. In turn, this cancer-induced reprogramming of AT2 cells promoted stem-like features in cancer cells and enhanced their initiation capacity. In conclusion, we propose the concept of "reflected stemness" as an early phenomenon during metastatic niche initiation, wherein metastatic cells reprogram the local tissue into a stem-like state that enhances intrinsic cancer-initiating potential, creating a positive feedback loop where tumorigenic programs are amplified.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
/
Tumor Microenvironment
/
Lung Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos