Scholarlink

<p>Metastatic breast cancer remains largely incurable, and the mechanisms driving the transition from primary to metastatic breast cancer remain elusive. We analyzed the complex landscape of estrogen receptor (ER)-positive breast cancer primary and metastatic tumors using scRNA-seq data from twenty-three female patients with either primary or metastatic disease. By employing single-cell transcriptional profiling of unpaired patient samples, we sought to elucidate the genetic and molecular mechanisms underlying changes in the metastatic tumor ecosystem. We identified specific subtypes of stromal and immune cells critical to forming a pro-tumor microenvironment in metastatic lesions, including CCL2+ macrophages, exhausted cytotoxic T cells, and FOXP3+ regulatory T cells. Analysis of cell-cell communication highlights a marked decrease in tumor-immune cell interactions in metastatic tissues, likely contributing to an immunosuppressive microenvironment. In contrast, primary breast cancer samples displayed increased activation of the TNF-α signaling pathway via NF-kB, indicating a potential therapeutic target. Our study comprehensively characterizes the transcriptional landscape encompassing primary and metastatic breast cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Single-cell RNA sequencing reveals different cellular states in malignant cells and the tumor microenvironment in primary and metastatic ER-positive breast cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月26日

查看全文
  • Furkan Ozmen,
  • Tugba Y. Ozmen,
  • Aysegul Ors,
  • Mahnaz Janghorban,
  • Matthew J. Rames,
  • Xi Li,
  • Aaron Reid Doe,
  • Fariba Behbod,
  • Gordon B. Mills,
  • Hisham Mohammed

摘要

Metastatic breast cancer remains largely incurable, and the mechanisms driving the transition from primary to metastatic breast cancer remain elusive. We analyzed the complex landscape of estrogen receptor (ER)-positive breast cancer primary and metastatic tumors using scRNA-seq data from twenty-three female patients with either primary or metastatic disease. By employing single-cell transcriptional profiling of unpaired patient samples, we sought to elucidate the genetic and molecular mechanisms underlying changes in the metastatic tumor ecosystem. We identified specific subtypes of stromal and immune cells critical to forming a pro-tumor microenvironment in metastatic lesions, including CCL2+ macrophages, exhausted cytotoxic T cells, and FOXP3+ regulatory T cells. Analysis of cell-cell communication highlights a marked decrease in tumor-immune cell interactions in metastatic tissues, likely contributing to an immunosuppressive microenvironment. In contrast, primary breast cancer samples displayed increased activation of the TNF-α signaling pathway via NF-kB, indicating a potential therapeutic target. Our study comprehensively characterizes the transcriptional landscape encompassing primary and metastatic breast cancer.