Unraveling the metastatic niche in breast cancer bone metastasis through single-cell RNA sequencing

Clinical and Translational Oncology Pub Date : 2024-07-27 DOI:10.1007/s12094-024-03594-2

Xiangyu Li, Ziyu Gao, Meiling Yang, Ciqiu Yang, Dongyang Yang, Wenhui Cui, Dandan Wu, Jie Zhou

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Abstract

Purpose

Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA.

Methods

This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM.

Results and Conclusions

Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent an initiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTN interactions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN, and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insights deepen our understanding of the metastatic niche in breast cancer BoM.

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通过单细胞 RNA 测序揭示乳腺癌骨转移的转移生态位

目的乳腺癌（BRCA）具有独特的转移模式，通常表现为骨转移（BoM），给临床带来了巨大挑战。本研究采用单细胞 RNA 测序和 TCGA 数据分析，对原发肿瘤（PT）、淋巴结转移（LN）和骨转移（BoM）进行了全面比较。结果与结论我们的研究发现了骨转移（BoM）中的转移龛，其特点是癌症相关成纤维细胞（CAFs）增多，免疫细胞减少。我们还发现了与不良预后相关的 BRCA BoM 细胞的独特亚型（状态 1）。状态 1 显示出更强的干性特征，可能代表了 BRCA BoM 的起始阶段。揭示了涉及肿瘤、基质和免疫细胞的复杂细胞通讯。FN1、SPP1和MDK的相互作用与BoM中免疫细胞的升高有关。CD46、MDK和PTN的相互作用推动了肌成纤维细胞的活化和增殖，从而导致组织重塑。此外，MDK、PTN 和 FN1 的相互作用会影响 FAP+ CAF 的活化，从而影响 BoM 中的细胞粘附和迁移。这些见解加深了我们对乳腺癌BoM转移龛的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Clinical and Translational Oncology

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