Tag: metastasis

Plant Virus-based Treatment Protects Against Lung Tumours

Image source: CDC/Unsplash

Using a virus that grows in black-eyed pea plants, nanoengineers developed a new treatment that could keep metastatic cancers at bay from the lungs. 

Not only did the treatment slow tumour growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimised the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published in Advanced Science.

Researchers developed an experimental treatment that combats metastatic spread. This involves a plant virus called the cowpea mosaic virus, harmless to animals and humans, but which the body still registers as a foreign invader, thus triggering an immune response that could also boost the body’s cancer-fighting ability.

The idea is to use the plant virus to help the body’s immune system recognise and destroy cancer cells in the lungs. The virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at the University of California San Diego.

To draw this immune response to lung tumours, Prof Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection in the lungs. Overexpression of S100A9 has been observed to play a role in tumour growth and spread.

“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Prof Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”

“Because these nanoparticles tend to localise in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering PhD student in Steinmetz’s lab who is one of the co-first authors on the paper.

To make the nanoparticles, the researchers infected black-eyed pea plants with cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then fixed S100A9-targeting molecules to the particles’ surfaces.

The researchers performed both prevention and treatment studies. In the prevention studies, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells into these mice. Treated mice showed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.

In the treatment studies, the researchers administered the nanoparticles to mice with metastatic tumours in their lungs. The treated mice exhibited smaller lung tumours and survived longer than untreated mice.

Prof Steinmetz envisions that the treatment could be useful after tumourectomy. “It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumours. Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis,” she said.

More detailed immunotoxicity and pharmacology studies are needed before this can progress to a treatment. Future studies will also explore combining this with standard cancer therapies such as chemotherapy.

Source: University of California – San Diego

Cells in the Centres of Kidney Tumours are The Most Aggressive

Researchers have found that cells from different parts of kidney tumours behave differently, and cells within the centre of a tumour are the most aggressive and most likely to spread around the body.

Metastasis, where cancer cells from tumours spread to other parts of the body, is the main cause of death in cancer patients. 

In this multidisciplinary study published in Nature Ecology and Evolution, scientists analysed 756 cancer biopsy samples from different regions within tumours from the TRACERx Renal study.

They discovered that, in contrast to the cells at the outside of tumours, the cells in the centres of tumours have more unstable genomes, and a higher potential for metastasis. The cells on the outside had lower growth rates and had less genetic damage.

“Cancer cells in the central zone of the tumour face harsh environmental conditions, as there’s a lack of blood supply and oxygen. They have to adapt to survive, which makes them stronger and more aggressive. This also means they are more likely to successfully evolve into cells that can disseminate and take hold in distant organs,” explained Kevin Litchfield, paper author and group leader at the UCL Cancer Institute.

These findings show that it is important to focus on the tumour centre for a better understanding of how cancer spreads, and identify the most dangerous cells. Also, in order to wipe out the most aggressive tumour cells, treatment development must target the unique environmental conditions found within the tumour core.

The scientists also examined how genetically different populations of cancer cells grow within a tumour. With a unique mapping tall that reconstructed the growth of tumour cells, they discovered that, while tumours tend to follow a pattern where populations of cells grow in the local area, in two cases, cells took hold in a new region of the tumour by seemingly ‘jumping’ over other populations of tumour cells.

For their next steps, the researchers aim to reconstruct 3D tumour maps, providing even better visualisation of the tumours’ internal structure.

Samra Turajlic, head of the Crick’s Cancer Dynamics Laboratory, Consultant Medical Oncologist at the Royal Marsden NHS Foundation Trust and the Chief Investigator of TRACERx Renal, said: “Cancer spread is one of the biggest barriers to improving survival rates. In the context of the TRACERx Renal study we previously resolved the genetic make up of different tumour areas, but until now, there has been no understanding of how these differences relate spatially. The most critical question is the part of the tumour from which cancer cells break away and migrate making cancer incurable.

“Using this unique clinical cohort and a multidisciplinary approach, including mathematical modeling, we identified with precision the place in the tumour where genetic chaos emerges to give rise to metastases. Our observations shed light on the sort of environmental conditions that would foster emergence of aggressive behaviour. These findings are a critical foundation for considering how we target or even prevent distinct populations of cells that pose the biggest threat.”

Source: Francis Crick Institute

Electromagnetic Fields Could Inhibit Breast Cancer Cell Spread

A new study has shown that electrical fields can slow, and in some cases halt, the spread of breast cancer cells through the body.

The research also found how electromagnetic fields (EMFs) have the ability to hinder the number of cancer cells that can spread. Pulsed EMFs have also been shown to have some effectiveness in pain management, and low level EMFs were shown also to reduce blood glucose in animal models, a possible first step to treating diabetes.

“We think we can hinder metastasis by applying these fields, but we also think it may be possible to even destroy tumours using this approach,” said senior author Vish Subramaniam, former professor of mechanical and aerospace engineering at The Ohio State University. Subramaniam retired from Ohio State in December.

“That is unclear at this stage, but we are working on understanding that – how big should the electromagnetic field be, how close should it be to the tumour? Those are the next questions we hope to answer,” he said.
Subramaniam said that this had the effect of the EMF is to slow down some of the cancer cells. “It makes some of them stop for a little while before they start to move, slowly, again. As a group, they appear to have split up. So how quickly the whole group is moving and for how long they are moving becomes affected.”

The effect was applied to human cancer cells in vitro and has not been applied in humans.

The EMFs seem to selectively slow down the cancer cells’ metabolism by affecting the electrical fields inside the individual cells—completely noninvasively and without side effects like ionising radiation, which would mean a revolutionary form of cancer treatment if it could be made to work in practice. This ability to access a cell’s internal workings is new to the study of how cancer metastasises, said Prof  Subramaniam.

“Now that we know this, we can start to answer other questions, too,” Subramaniam said. “How do we affect the metabolism to the point that we not only make it not move but we choke it, we completely starve it. Or can we slow it down to the point where it will always remain weak?”

Source: News-Medical.Net

Journal information: Jones, T.H., et al. (2021) Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity. Bioelectricity. doi.org/10.1089/bioe.2020.0048.