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

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 () and Lonnie D. Shea ()
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Jing Wang: University of Michigan
Ramon Ocadiz-Ruiz: University of Michigan
Matthew S. Hall: University of Michigan
Grace G. Bushnell: University of Michigan
Sophia M. Orbach: University of Michigan
Joseph T. Decker: University of Michigan
Ravi M. Raghani: University of Michigan
Yining Zhang: University of Michigan
Aaron H. Morris: University of Michigan
Jacqueline S. Jeruss: University of Michigan
Lonnie D. Shea: University of Michigan

Nature Communications, 2023, vol. 14, issue 1, 1-20

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.

Date: 2023
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DOI: 10.1038/s41467-023-40478-5

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