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A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs

Authors :
Jing Wang
Ramon Ocadiz-Ruiz
Matthew S. Hall
Grace G. Bushnell
Sophia M. Orbach
Joseph T. Decker
Ravi M. Raghani
Yining Zhang
Aaron H. Morris
Jacqueline S. Jeruss
Lonnie D. Shea
Source :
Nature Communications, Vol 14, Iss 1, Pp 1-20 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tropic circulating tumor cells yet suppresses their growth through potent in situ antitumor immunity. In contrast, the lung, the endogenous metastatic organ for these models, develops lethal metastases in aggressive breast cancer, with less aggressive tumor models developing dormant lungs suppressing tumor growth. Our study reveals multifaceted roles of neutrophils in regulating metastasis. Breast cancer-educated neutrophils infiltrate the scaffold implants and lungs, secreting the same signal to attract lung-tropic circulating tumor cells. Second, antitumor and pro-tumor neutrophils are selectively recruited to the dormant scaffolds and lungs, respectively, responding to distinct groups of chemoattractants to establish activated or suppressive immune environments that direct different fates of cancer cells.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.7ceec19b147f4e66ae168caae2f3b2a2
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-023-40478-5