Work

Matrix-state switching in osteosarcoma under therapeutic pressure: integrin rewiring, residual disease, and pulmonary niche adaptation

Year: 2026

Type: review

Abstract: Osteosarcoma cells encounter distinct extracellular environments during primary growth, treatment, detachment, and pulmonary colonization. A single constitutive extracellular-matrix (ECM)-integrin-FAK-AKT pathway therefore cannot explain residual disease and metastasis. This Review proposes matrix-state switching as a stage-resolved framework jointly defined by ligand presentation, adhesion-receptor usage, matrix-coupled signaling dependencies, and the cellular compartment sustaining these interactions. The framework is not an obligatory linear trajectory: observed state differences may reflect reversible adaptation, selection of pre-existing populations, therapy-associated remodeling, or combinations thereof. Primary lesions show component-selective matrix-conditioned drug tolerance; detached cells can preserve Src-dependent PI3K-AKT survival despite loss of sustained FAK and paxillin phosphorylation; and pulmonary colonization introduces distinct tumor-cell and stromal dependencies, including β4-ezrin-associated signaling and the CXCL14-α11β1 fibroblast circuit. Recent single-cell and spatial studies further indicate therapy-associated ECM remodeling and residual malignant-cell programs involving stemness, epithelial-mesenchymal transition, ECM interaction, and PI3K signaling, but do not establish same-clone longitudinal switching. LAMC1 is evaluated strictly as a hypothesis-generating matrix-state candidate because current osteosarcoma-specific evidence remains transcript-level. We position matrix-state switching as a matrix- and adhesion-focused layer within the broader communication-driven osteosarcoma ecosystem and define falsifiable criteria for distinguishing functional state dependencies from association.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1987843

Authors: Yang Gu, Yunqiang Zhuang, Wei Zhang

Institution: Ningbo No.6 Hospital

Language: English

Topic: Sarcoma Diagnosis and Treatment

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801