Generation of 3D melanoma models using an assembloid-based approach.

Area of Science:

• Oncology
• Biomedical Engineering
• 3D Cell Culture

Background:

• Traditional 3D tumor models often fail to fully replicate the complex tumor microenvironment.
• There is a need for more biologically relevant models to study cancer progression and test therapeutics.
• Existing models lack sufficient recapitulation of cellular crosstalk, tumor aggressiveness, and invasion.

Purpose of the Study:

• To develop a novel, self-organizing, heterotypic 3D melanoma model using assembloids.
• To better mimic the tumor microenvironment, including cellular crosstalk and tumor aggressiveness.
• To assess the model's invasiveness, stem-cell-like features, and drug sensitivity.

Main Methods:

• Construction of melanoma assembloids by fusing individual stromal multicellular spheroids (MCSs).
• Analysis of tumor cell stemness markers (SOX2, POU5F1, NANOG).
• Assessment of invasiveness in 3D matrices and sensitivity to doxorubicin.

Main Results:

• The developed assembloids exhibit self-organizing, heterotypic characteristics.
• Melanoma cells within the assembloids display stem-cell-like features with up-regulated pluripotency regulators.
• Assembloids demonstrate high invasiveness, promoted by stromal cells via metalloproteinase production.
• The model shows sensitivity to the anticancer drug doxorubicin.

Conclusions:

• Melanoma assembloids offer a more biosimilar 3D cancer model compared to traditional MCSs.
• This model closely mimics the tumor microenvironment, aiding the study of tumor progression.
• The approach provides a route for superior tumor models with enhanced similarity to native cancer tissues for drug screening and research.