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Updated: Sep 24, 2025
Monitoring Cancer Cell Invasion and T-Cell Cytotoxicity in 3D Culture
Published on: June 23, 2020
A novel 3D co-culture platform for integrating tissue interfaces for tumor growth, migration and therapeutic
Mansoureh Mohseni Garakani1, Pouyan Ahangar2, Sean Watson3
1Chemical Engineering Department, Polytechnique Montreal, Canada; Institute of Biomedical Engineering, Polytechnique Montreal, Canada.
Abstract:
Metastatic cancers can be highly heterogeneous, show large patient variability and are typically hard to treat due to chemoresistance. Personalized therapies are therefore needed to suppress tumor growth and enhance patient's quality of life. Identifying appropriate patient-specific therapies remains a challenge though, due mainly to non-physiological in vitro culture systems. Therefore, more complex and physiological in vitro human cancer microenvironment tools could drastically aid in development of new therapies. We developed a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that can mimic the human cancer microenvironment for customized-cancer therapeutic screening. The PP-3D-S was characterized for optimal plasma-modifying treatment and scaffolds morphology including fiber diameter and pore size. PP-3D-S was then seeded with human fibroblasts to mimic a stromal tissue layer; cell adhesion on plasma-modified poly (lactic acid), PLA, electrospun mats vastly exceeded that on untreated controls. The cell-seeded scaffolds were then overlaid with alginate/gelatin-based hydrogel embedded with MDA-MB231 human breast cancer cells, representing a tumor-tissue interface. Among three different plasma treatments, we found that NH3 plasma promoted the most tumor cell migration to the scaffold surfaces after 7 days of culture. For all treated and non-treated mats, we observed a significant difference in tumor cell migration between small-sized and either medium- or large-sized scaffolds. In addition, we found that the PP-3D-S was highly comparable to the standard Matrigel® migration assays in two different sets of doxorubicin screening experiments, where 75% reduction in migration was achieved with 0.5 μM doxorubicin for both systems. Taken together, our data indicate that PP-3D-S is an effective, low-cost, and easy-to-use alternate 3D tumor migration model which may be suitable as a physiological drug screening tool for personalized medicine against metastatic cancers.
Insights
Researchers developed a novel 3D scaffold that mimics the human cancer microenvironment. This tool aids in personalized cancer therapy screening and drug development for metastatic cancers.
Area of Science:
- Biomaterials Engineering
- Cancer Research
- Tissue Engineering
Background:
- Metastatic cancers are heterogeneous and difficult to treat due to chemoresistance.
- Current in vitro models do not accurately replicate the human cancer microenvironment, hindering personalized therapy development.
- There is a need for advanced in vitro tools that mimic physiological conditions for effective therapeutic screening.
Purpose of the Study:
- To develop and characterize a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that mimics the human cancer microenvironment.
- To evaluate the PP-3D-S as a platform for customized cancer therapeutic screening and drug development.
- To assess the efficacy of the PP-3D-S in modeling tumor cell migration and drug response.
Main Methods:
- Fabrication and characterization of plasma-modified, electro-spun poly (lactic acid) scaffolds (PP-3D-S).
- Seeding scaffolds with human fibroblasts to create a stromal layer, followed by overlaying with a hydrogel containing MDA-MB231 breast cancer cells.
- Evaluating cell adhesion, tumor cell migration under different plasma treatments and scaffold sizes, and drug screening (doxorubicin) using the PP-3D-S model.
Main Results:
- Plasma modification, particularly with NH3, significantly enhanced cell adhesion and promoted tumor cell migration on the PP-3D-S.
- Scaffold size influenced tumor cell migration, with significant differences observed between small and larger scaffolds.
- The PP-3D-S model demonstrated comparable results to standard Matrigel® assays in doxorubicin drug screening, showing a 75% reduction in migration at 0.5 μM.
Conclusions:
- The developed PP-3D-S is an effective, low-cost, and user-friendly 3D model that accurately mimics the human cancer microenvironment.
- This scaffold shows promise as a physiological drug screening tool for personalized medicine against metastatic cancers.
- The PP-3D-S facilitates the study of tumor cell migration and response to therapies, aiding in the development of targeted treatments.
