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<p>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.</p>

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Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness

  • 期刊论文

  • 发表日期：

    2025年3月7日

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  • Sandra Camargo,
  • Ori Moskowitz,
  • Amir Giladi,
  • Maiia Levinson,
  • Roi Balaban,
  • Shani Gola,
  • Alice Raizman,
  • Kelly Lipczyc,
  • Alon Richter,
  • Noa Keren-Khadmy,
  • Oren Barboy,
  • Yael Dugach,
  • Yaron Carmi,
  • Amir Sonnenblick,
  • Merav Cohen

摘要

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.