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

TL;DR

Researchers created a new lung cancer cell line that strongly metastasizes to bones, which could help improve treatments for lung cancer patients.

Contribution

A novel bone-metastatic subline of A549 cells, A549-BM5, was developed with enhanced bone tropism and utility for studying metastasis mechanisms.

Findings

A549-BM5 cells showed increased migration, invasion, and bone colonization in mouse models.

The cells disrupted bone homeostasis by promoting osteoblast and osteoclast activity.

Transcriptomic and proteomic analyses identified dysregulated pathways like EMT and bone morphogenesis.

Abstract

•A549-BM5, a bone-metastatic subline of A549, was established through in vivo selection.•The model facilitates investigation of mechanisms underlying NSCLC bone metastasis.•Findings may assist in developing strategies to improve outcomes for lung cancer patients.

A549-BM5, a bone-metastatic subline of A549, was established through in vivo selection.

The model facilitates investigation of mechanisms underlying NSCLC bone metastasis.

Findings may assist in developing strategies to improve outcomes for lung cancer patients.

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.

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