WCLC 2025 - Posters & ePosters-PT1.02.02 Novel Organoid Models of Patient-Derived Lung Cancer in Decellularized Mouse Lung Tissue

Pdf Summary

This study presents novel organoid models of patient-derived lung cancer developed using decellularized mouse lung tissue (DCL) to better mimic the tumor microenvironment. Traditional studies of lung cancer tumorigenicity and response to extracellular matrix (ECM) protein combinations have been limited by the complexity of in vitro systems. To address this, the authors created a culture system using acellular normal mouse lung tissue as a 3D scaffold that preserves native ECM components.<br /><br />The method involved decellularizing mouse lungs to remove cells while retaining the ECM structure and proteins such as Fibrillin 2 and Tenascin C, which were shown to enhance tumor cell coverage. Patient-derived xenograft (PDX) tumor cells and primary lung cancer cells were seeded onto these scaffolds to create ex vivo organoid models, termed XDC and XDO, that exploit the physiological ECM environment. The DCL models supported robust growth of PDX tumor cells, demonstrated with mCherry fluorescence tracking. <br /><br />N-glycosylation-based enrichment techniques were used to characterize ECM protein origin from both mouse and human components, confirming matrix remodeling in these models. Functional studies showed that an EGFR exon 19 deletion mutant in the XDC137 model responded to tyrosine kinase inhibitors, indicating potential for therapeutic testing.<br /><br />Overall, this DCL-based platform complements existing organoid technologies by providing a more physiologically relevant stromal matrix that closely mimics patient tumors. This approach could advance lung cancer research by enabling more accurate studies of tumor-ECM interactions and drug responses. The work is supported by references to recent advances in tissue engineering and cancer modeling, highlighting the innovation in combining decellularized tissue scaffolds with patient-derived tumor cells.  <br /><br />In conclusion, decellularized lung scaffolds offer a promising new ex vivo model system to study lung cancer biology and therapeutic responses within a native-like microenvironment.

Asset Subtitle

Roya Navab

Meta Tag

Speaker Roya Navab

Topic Tumor Biology – Preclinical Biology

Keywords

lung cancer

organoid models

decellularized lung tissue

extracellular matrix

patient-derived xenograft

3D scaffold

tumor microenvironment

ECM protein remodeling

tyrosine kinase inhibitors

tissue engineering