@article{572dc944d625491892ffd25d4853774e,
title = "Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness",
abstract = "Tissue remodeling and cell plasticity in the mammary gland are activated by multilineage communications; however, the dynamic signaling promoting breast cancer remains unclear. Here, by RNA sequencing of single cells and physically interacting cells (PICs) along mammary gland development and carcinogenesis, we uncovered that neutrophils appear transiently during early development and re-emerge in physical interaction with tumor cells in advanced carcinoma. Neutrophil heterogeneity analysis characterized transcriptional states linked to age and cancer stage. Integrating ligand–receptor and PIC sequencing analyses with various functional experiments unveiled a physical and secreted protumorigenic signaling niche. This approach revealed that neutrophils are recruited by tumor-activated macrophages and physically interact with tumor cells, increasing tumor cell proliferative and invasive properties, as well as endothelial proliferation and angiogenesis. The molecular program upregulated in neutrophil-PICs correlates with lower survival in advanced breast cancer patients. Our interaction-driven perspective highlights potential molecular targets and biomarkers for breast cancer treatment.",
author = "Sandra Camargo and Ori Moskowitz and Amir Giladi and Maiia Levinson and Roi Balaban and Shani Gola and Alice Raizman and Kelly Lipczyc and Alon Richter and Noa Keren-Khadmy and Oren Barboy and Yael Dugach and Yaron Carmi and Amir Sonnenblick and Merav Cohen",
note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.",
year = "2025",
month = mar,
doi = "10.1038/s43018-025-00924-3",
language = "אנגלית",
volume = "6",
pages = "540--558",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "3",
}
