A vascularized 3D bioengineered lung tumor model for anticancer drug screening

Area of Science:

• Biomedical Engineering
• Cancer Research
• 3D Cell Culture Models

Background:

• Preclinical anticancer drug efficacy has limited clinical translation due to inadequate models.
• Existing 3D tumor models often lack vascularization, a key factor in tumor progression and treatment resistance.

Purpose of the Study:

• To develop a vascularized 3D lung cancer model that accurately replicates the tumor microenvironment.
• To assess the model's utility for investigating non-small cell lung cancer (NSCLC) progression and drug response.

Main Methods:

• Co-seeding a decellularized lung scaffold with endothelial cells, pericytes, and A549 adenocarcinoma cells to create a tri-culture system.
• Characterizing the vascular network, tumor microenvironment features (hypoxia, LOX, desmoplastic niches), and cellular behaviors.
• Integrating patient-derived lung cancer organoids for drug response testing.

Main Results:

• The tri-culture system formed a hierarchical vascular network and recapitulated key tumor microenvironment features.
• The 3D vascularized model showed enhanced cell migration, MUC5AC hypersecretion, and reduced chemosensitivity compared to traditional cultures.
• Hypoxia-activated HIF-1α/LOX signaling promoted extracellular matrix remodeling, creating a chemoprotective niche.

Conclusions:

• The vascularized 3D lung cancer model provides a physiologically relevant platform for studying NSCLC.
• This model facilitates investigation of tumor progression and optimization of patient-specific drug screening.