Huntsman Cancer Institute, and.
Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
J Clin Invest. 2024 Sep 3;134(17):e183971. doi: 10.1172/JCI183971.
Many aspects of breast cancer metastasis remain poorly understood, despite its clinical importance. In this issue of the JCI, Winkler et al. have applied an elegant patient-derived xenograft (PDX) model to map the transcriptomes of single cells in matched primary tumors and lung metastases across 13 breast cancer PDX models. They identified distinct transcriptional changes associated with metastatic evolution in lowly and highly metastatic primary tumors. Furthermore, by classifying the "epithelial-mesenchymal plasticity" (EMP) state of single cells, they revealed that considerable EMP heterogeneity exists among primary and metastatic human breast cancer cells. However, the EMP profile of a tumor does not change substantially upon metastasis. These findings give an unprecedentedly detailed view into the transcriptional heterogeneity and evolution of metastatic human breast cancer.
尽管乳腺癌转移具有重要的临床意义，但仍有许多方面尚未被充分了解。在本期 JCI 中，Winkler 等人应用了一种精巧的患者来源异种移植（PDX）模型，对 13 种乳腺癌 PDX 模型中的配对原发肿瘤和肺转移灶中的单细胞转录组进行了图谱绘制。他们鉴定出与原发肿瘤中低度和高度转移性肿瘤的转移进化相关的独特转录变化。此外，通过对单细胞的“上皮-间充质可塑性”（EMP）状态进行分类，他们揭示了原发和转移性人类乳腺癌细胞之间存在相当大的 EMP 异质性。然而，肿瘤的 EMP 特征在转移后并没有发生实质性改变。这些发现为转移性人类乳腺癌的转录异质性和进化提供了前所未有的详细视图。
