对 bulk 和单细胞测序数据的综合分析揭示,EMP1/COL3A1 成纤维细胞有助于乳腺癌、前列腺癌和肾癌的骨转移过程。

An integrated analysis of bulk and single-cell sequencing data reveals that EMP1/COL3A1 fibroblasts contribute to the bone metastasis process in breast, prostate, and renal cancers.

机构信息

Department of Orthopedics and Joints, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.

Department of Breast Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.

出版信息

Front Immunol. 2023 Dec 19;14:1313536. doi: 10.3389/fimmu.2023.1313536. eCollection 2023.

Abstract

INTRODUCTION

Bone metastasis (BoM) occurs when cancer cells spread from their primary sites to a bone. Currently, the mechanism underlying this metastasis process remains unclear.

METHODS

In this project, through an integrated analysis of bulk-sequencing and single-cell RNA transcriptomic data, we explored the BoM-related features in tumor microenvironments of different tumors.

RESULTS

We first identified 34 up-regulated genes during the BoM process in breast cancer, and further explored their expression status among different components in the tumor microenvironment (TME) of BoM samples. Enriched EMP1+ fibroblasts were found in BoM samples, and a COL3A1-ADGRG1 communication between these fibroblasts and cancer cells was identified which might facilitate the BoM process. Moreover, a significant correlation between EMP1 and COL3A1 was identified in these fibroblasts, confirming the potential connection of these genes during the BoM process. Furthermore, the existence of these EMP1+/COL3A1+ fibroblasts was also verified in prostate cancer and renal cancer BoM samples, suggesting the importance of these fibroblasts from a pan-cancer perspective.

DISCUSSION

This study is the first attempt to investigate the relationship between fibroblasts and BoM process across multi-tumor TMEs. Our findings contribute another perspective in the exploration of BoM mechanism while providing some potential targets for future treatments of tumor metastasis.

摘要

简介

当癌细胞从原发部位扩散到骨骼时,就会发生骨转移(BoM)。目前,这种转移过程的机制尚不清楚。

方法

在这个项目中,我们通过对批量测序和单细胞 RNA 转录组数据的综合分析,探讨了不同肿瘤的肿瘤微环境中与 BoM 相关的特征。

结果

我们首先在乳腺癌的 BoM 过程中鉴定出 34 个上调基因,并进一步探索了它们在 BoM 样本肿瘤微环境(TME)不同成分中的表达状态。在 BoM 样本中发现了丰富的 EMP1+成纤维细胞,并且鉴定出这些成纤维细胞与癌细胞之间存在 COL3A1-ADGRG1 通讯,这可能促进了 BoM 过程。此外,在这些成纤维细胞中还鉴定到 EMP1 和 COL3A1 之间存在显著相关性,证实了这些基因在 BoM 过程中的潜在联系。此外,在前列腺癌和肾癌的 BoM 样本中也验证了这些 EMP1+/COL3A1+成纤维细胞的存在,从泛癌的角度来看,这些成纤维细胞的重要性不言而喻。

讨论

本研究首次尝试在多肿瘤 TME 中研究成纤维细胞与 BoM 过程之间的关系。我们的研究结果为探索 BoM 机制提供了另一个视角,同时为未来肿瘤转移的治疗提供了一些潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/10770257/72817d502379/fimmu-14-1313536-g001.jpg

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