Establishment and comprehensive characterization of a subline with highly bone-metastatic propensity derived from the lung adenocarcinoma A549 cell line

IF 3.5 2区医学 Q2 Medicine

Journal of Bone Oncology Pub Date : 2025-10-22 DOI:10.1016/j.jbo.2025.100719

Yujian Xu , Yahan Qin , Wenjun Chai , Ke Xue , Xiaoli Liu , Jing Li , Yue Cao , Lei Sun , Hongyu Pan , Mingxia Yan

{"title":"Establishment and comprehensive characterization of a subline with highly bone-metastatic propensity derived from the lung adenocarcinoma A549 cell line","authors":"Yujian Xu , Yahan Qin , Wenjun Chai , Ke Xue , Xiaoli Liu , Jing Li , Yue Cao , Lei Sun , Hongyu Pan , Mingxia Yan","doi":"10.1016/j.jbo.2025.100719","DOIUrl":null,"url":null,"abstract":"<div><div>Bone metastasis is a major cause of mortality in lung adenocarcinoma, but the mechanisms remain poorly understood. Here, we established a highly bone-metastatic subline, A549-BM5, from the A549 cell line through five rounds of <em>in vivo</em> selection. A549-BM5 cells exhibited enhanced migration and invasion, and preferentially colonized specific skeletal sites in mouse models. In the bone microenvironment, they promoted the recruitment and differentiation of osteoblasts and osteoclasts, disrupting bone homeostasis. Transcriptomic and proteomic profiling revealed dysregulation in pathways such as EMT, adhesion, and bone morphogenesis. We further applied a random forest model to identify potential therapeutic targets associated with bone metastasis. Compared to existing A549-based models, A549-BM5 offers earlier metastasis onset, stable bone tropism, and broader interaction with the bone niche. This model provides a valuable platform for mechanistic studies and therapeutic development targeting lung cancer bone metastasis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100719"},"PeriodicalIF":3.5000,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bone Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212137425000600","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Bone metastasis is a major cause of mortality in lung adenocarcinoma, but the mechanisms remain poorly understood. Here, we established a highly bone-metastatic subline, A549-BM5, from the A549 cell line through five rounds of in vivo selection. A549-BM5 cells exhibited enhanced migration and invasion, and preferentially colonized specific skeletal sites in mouse models. In the bone microenvironment, they promoted the recruitment and differentiation of osteoblasts and osteoclasts, disrupting bone homeostasis. Transcriptomic and proteomic profiling revealed dysregulation in pathways such as EMT, adhesion, and bone morphogenesis. We further applied a random forest model to identify potential therapeutic targets associated with bone metastasis. Compared to existing A549-based models, A549-BM5 offers earlier metastasis onset, stable bone tropism, and broader interaction with the bone niche. This model provides a valuable platform for mechanistic studies and therapeutic development targeting lung cancer bone metastasis.

Abstract Image

查看原文本刊更多论文

从肺腺癌A549细胞系衍生的具有高度骨转移倾向的亚系的建立和综合表征

骨转移是肺腺癌死亡的主要原因，但其机制尚不清楚。在这里，我们从A549细胞系中通过五轮体内选择建立了一个高度骨转移亚系A549- bm5。在小鼠模型中，A549-BM5细胞表现出增强的迁移和侵袭，并优先定植特定的骨骼部位。在骨微环境中，它们促进成骨细胞和破骨细胞的募集和分化，破坏骨稳态。转录组学和蛋白质组学分析揭示了EMT、粘附和骨形态发生等途径的失调。我们进一步应用随机森林模型来确定与骨转移相关的潜在治疗靶点。与现有的基于a549的模型相比，A549-BM5具有更早的转移发生、稳定的骨向性以及与骨生态更广泛的相互作用。该模型为肺癌骨转移的机制研究和治疗开发提供了一个有价值的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Bone Oncology ONCOLOGY-

CiteScore

7.20

自引率

2.90%

发文量

审稿时长

34 days

期刊介绍： The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer. As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject. The areas covered by the journal include: Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment) Preclinical models of metastasis Bone microenvironment in cancer (stem cell, bone cell and cancer interactions) Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics) Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management) Bone imaging (clinical and animal, skeletal interventional radiology) Bone biomarkers (clinical and translational applications) Radiotherapy and radio-isotopes Skeletal complications Bone pain (mechanisms and management) Orthopaedic cancer surgery Primary bone tumours Clinical guidelines Multidisciplinary care Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.