Cancer model systems are available to investigate disease mechanisms and to screen therapies. However, two-dimensional (2D) tissue culture models may lack realistic complexity, and may not always show the entire picture needed to improve understanding and treatment of disease. Now, an international team led by the University of Nottingham and Queen Mary University London report they have created a multicellular 3D microenvironment that recreates the way tumor cells grow in ovarian cancer and respond to chemotherapy drugs.

Their study, “Peptide-protein co-assembling matrices as a biomimetic 3D model of ovarian cancer,” was published in Science Advances and led by Alvaro Mata, PhD, professor at the University of Nottingham’s School of Pharmacy.

“There is a need for improved three-dimensional (3D) cancer models to study tumor growth and progression as seen in patients and to test responses to new treatments,” noted the researchers.

The team reported that 90% of successful cancer treatments tested preclinically fail in the early phases of clinical trials, and less than 5% of oncology drugs are successful in clinical trials. Key features of tumor tissues such as cellular heterogeneity, presence of spheroids, and cross-talk with other cell types, are not recapitulated by conventional 2D cell cultures.

The researchers used peptide amphiphiles (PAs) to co-assemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. The matrix was designed to mimic physical and biomolecular features of tumors present in patients.

The new hydrogel biomaterial is made by the assembly of peptides with proteins found in ovarian cancer. “We included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells.”

Cancer spheroids made from triple cultures including ovarian cancer cells, endothelial cells, and mesenchymal stem cells growing within the peptide-protein co-assembling material. [Alvaro Mata]

“Bioengineered self-assembling matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner,” explained Mata. “…We tested the response of the lab grown tumors using chemotherapeutics to validate the functionality of the multicellular constructs and saw the tumor shrink. This suggests that the new peptide/protein/cellular biomaterial could lead to more effective testing of new drugs and treatments for ovarian cancer.”

3D cell cultures have been reported to regain intrinsic properties and to better mimic the in vivo situation than cells cultured as monolayers on plastic. Previous studies have shown that the gene expression profiles as well as the responses to treatment in the multicellular spheroid 3D models resemble more closely the in vivo situation.

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