A new, three-dimensional approach to cancer research

Model developed in Ireland better mimics environment cancer cells normally grow in

A 3D image showing neuroblastoma cells performing a ‘handshake’; that is physically interacting with each other

A 3D image showing neuroblastoma cells performing a ‘handshake’; that is physically interacting with each other

 

Scientists at the Royal College of Surgeons Ireland have established a new way of growing cancer cells in the laboratory that could speed up development of new drugs to fight cancer. The secret? It’s all about saying goodbye to flat research and finding your 3D groove.

The researchers have demonstrated cancer cells grown in 3D respond to treatment with chemotherapy in a similar way to tumours growing inside the body. Their work was recently published in the scientific journal Acta Biomaterialia.

Dr Olga Piskareva, leading childhood cancer researcher at RCSI explains that most experiments carried out in the laboratory involve cancer cells cultured on a flat surface, limiting the amount of information we can obtain from them.

“This approach has been useful to find new drugs which we now use in anticancer treatment, for example, but it still doesn’t mimic the actual environment where cells come from,” she says. Dr Piskareva, whose work is funded by the National Children’s Research Centre, believes that if scientists can grow cells in an environment which is closer – at least in the geometry perspective – to what happens in the body, this will seriously improve the drug screening process, increasing the chances of finding effective drugs or drug combinations to fight cancer.

“Cells grow in the body in three dimensions,” says Dr Piskareva, “because our body has height, width and depth [and this is true for] every single part and every single building block of the body such as cells. When we take the cells and grow them in flasks in the lab, cells lose one dimension, because they grow on a flat surface.”

Dr Piskareva explains that the model developed in her laboratory mimics the environment cells normally live in. “We have a scaffold which to some extent looks like a sponge, made from collagen. We use collagen because it is a natural protein that provides strength and structure to our bodies in three dimensions. We then load the cells on these sponges; they soak and start to grow.”

“Collagen scaffolds [provide] a natural three-dimensional environment. So, when we load cells, they attach to collagen and grow like grapes, mimicking what happens in the body. When we treat them with a drug, the treatment mimics reality.”

This model would show scientists how well prospective drugs work before they are tested in animal models. Using the current “flat” model, many drugs that look promising in the cell culture stage fail when they are tested in animals because cells growing in two dimensions react to drugs differently from when they grow in 3D. Testing the drugs in a 3D cell culture model will help identify the drugs that have the better chance of working in animals, eliminating a lot of unnecessary testing.

“This model helps to reduce the number of animals that we can use, because we can see if our drug responds differently in the 3D system in comparison with our traditional “flat” culture system,” Dr Piskareva says. This model can also help test different drug combinations as well as single drugs.

“Originally these scaffolds were developed for bone tissue regeneration by our collaborators at RCSI Tissue Engineering and Research Group (TERG), who are trying to figure out how they can use different materials of natural and artificial origin to recreate a scaffold that can temporarily mimic bone.”

“If you have a fracture/crack in the bone and you put one of these sponges inside, it’ll make a temporary plug which will accelerate growth of bone tissue and help heal bone much faster,” Dr Piskareva says. So from bone regeneration to helping with the development of new anti-cancer drugs: this is a good example of how research can uncover new uses of existing knowledge and technology.

Dr Piskareva notes that that this is a minimal model of our tissue, because in reality there are not just cancer cells inside a tumour. “With this model you can increase complexity by adding different types of cells, such as cells that form the blood vessels . . .You will have a two-cell type system and can investigate how blood vessel cells interact with cancer cells and how drugs that try to cut blood flow to cancer cells could affect cancer cell growth.”

The next step for Dr Piskareva’s team is to try and reconstruct tumour microenvironment using the scaffolds by incorporating more non-cancerous cell types and structural molecules that form the native tumour.

“On the other side, these scaffolds could help if you take a biopsy from a patient, disintegrate the cells, load them on our scaffold and see which drugs are beneficial for a particular patient and at which dose. We will be able to predict which drug or combination of drugs would be beneficial for a patient,” she says.

The personalised medicine approach is a hot topic at the moment, but is it feasible? “It might take some time, but it’s possible, because there are [already] models like these in mice, and these biopsies respond in exactly the same fashion as tumours in the patient.” However, as Dr Piskareva points out, these tests could be run in the scaffolds and there would be no need to use any animals for them.

Although the discovery could be applicable in principle to any solid tumour, Dr Piskareva’s target is neuroblastoma, a relatively common child cancer which affects a specific type of nerve cells in unborn children. “It’s quite aggressive and unfortunately there are many children who have metastasis when they are diagnosed, and this is the most challenging group to treat.”

She points out that children are not small adults; the same is true about their cancers. “It is very interesting that some types of cancers which we see in adults don’t exist in children and vice versa. When adults are diagnosed with cancer we know that the risk factors are usually due to lifestyle habits or social environment; in children we don’t know, which makes it worse because we can’t predict it.”

No one knows why neuroblastoma happens and quickly spread to other parts of the body. “We have to understand how and why neuroblastoma cells spread, so we can identify the weaknesses that we can target to stop the metastatic process. This new 3D scaffold based tumour model is a promising tool to make it happen faster.”