CD146⁺ pericyte-like lung cancer brain metastatic stem cells promote tumor angiogenesis through dual regulatory effects on the VEGF/VEGFR axis.

ABSTRACT: Rationale: Anti-angiogenic therapy is indispensable for the treatment of non-small cell lung carcinoma (NSCLC)-derived brain metastasis (BrM). Targeting vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is the most effective strategy against angiogenesis. However, bevacizumab (Bev) shows limited therapeutic effects on NSCLC BrM. The plasticity of cancer stem cells (CSCs) has been found to drive therapeutic resistance via the "mimicry" behavior. Methods: CD146⁺ BrM-CSCs were validated in clinical tissues and organoids using immunostaining assays. The ability of CD146⁺ BrM-CSCs to induce angiogenesis was examined using an ex vivo multi-organ microfluidic bionic chip and animal models. The effects of CD146 on the VEGF and VEGFR were

SUBMITTER: Liu W 

PROVIDER: S-EPMC12680595 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature