Back to Search
Start Over
Stress-Inducible Gene
- Source :
- International Journal of Molecular Sciences
- Publication Year :
- 2021
-
Abstract
- Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung.
- Subjects :
- Lung Neoplasms
lung colonization
Genotype
Mice, Inbred Strains
Mice, Transgenic
chemotherapy
Article
Mice
Genes, Reporter
Stress, Physiological
Cathelicidins
breast cancer metastasis
Cell Line, Tumor
Tumor-Associated Macrophages
Tumor Microenvironment
Animals
Humans
Atf3
Neoplasm Metastasis
Cyclophosphamide
Mice, Knockout
Activating Transcription Factor 3
Macrophages
Transendothelial and Transepithelial Migration
Mammary Neoplasms, Experimental
stress response
respiratory system
Macrophage Activation
Neoadjuvant Therapy
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Neoplastic Stem Cells
macrophage dichotomy
Neoplasm Transplantation
Antimicrobial Cationic Peptides
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.pmid..........7f6c838240be3f7ad9d919d76a9a9e5e