After an extensive study of breast cancer cell shapes, scientists conclude they can influence a tumor’s response to treatment – such as making it more or less vulnerable to attack by the immune system.
Writing in the journal Molecular Systems Biology, researchers from the Institute of Cancer Research in London, UK, describe how they used robotic microscopy and mathematical algorithms – not unlike the algorithms Facebook uses for facial recognition – to assess shape and contextual features of hundreds of thousands of cancer cells.
The study highlights the fact that the body’s natural defenses are constantly battling against cancer cells, and there are numerous strategies on both sides of the fight. Health wins when the balance tips one way – disease wins when it tips the other way.
The study shows that the physical shape of a cancer cell can be one of the things that tips the balance in favor of disease – not only by helping it to evade the immune system but even to the point of helping it thrive in response to it.
Lead researcher Dr. Chris Bakal, who heads the Dynamic Cell Systems team at the ICR, explains the crux of their findings:
“Our study shows the crucial importance of a breast cancer cell’s shape in how it responds to inflammation – with certain shapes more likely to respond to the body’s immune system by activating pro-survival signals.”
He and his colleagues suggest that changing the shape of cancer cells – either mechanically, chemically or genetically – could help tip the balance against the tumor by using the inflammatory response in the body’s own immune system to fight cancer.
In their work, the team has focused on the activity of a protein called nuclear factor kappa B (NF-kappaB), a key player in inflammation. There is a lot of evidence that this protein misbehaves in many cancers – it sends out signals that promote survival of the cell – and that suppressing it stops cancer cells proliferating.
However, the researchers note that while we know a lot about the signaling events surrounding the aberrant behavior of NF-kappaB, we know little about how the physical properties of the cell itself and its environment might affect it.
For their study, the researchers measured a total of 77 cell shape and environmental features – such as how close a cell is to its neighbors – in more than 307,000 breast cancer cells. To assess shape they measured features like how round the cells were, the ratio of their length to their width, plus the extent of their protrusions and “ruffliness.”
From the results the researchers saw that – depending on the levels of NF-kappaB in their nuclei – the cells fell mostly into two main groups: mesenchymal-like and epithelial-like.
Mesenchymal-like breast cancer cells had more NF-kappaB in their nuclei, tended to be larger and more “ruffly”, with many more sharp protrusions than epithelial-like cells, which are normally softer-edged and rounder.
A key discovery was finding that an inflammatory signal called TNFalpha was a strong trigger for the NF-kappaB pro-survival signal in the mesenchymal-like cells, but was only weakly activated in the epithelial-like cells.
Using detailed mathematical modeling, the team also showed how aspects of cell shape influence the transfer of NF-kappaB into and out of cell nuclei under the control of TNFalpha signals.
In the following video, Dr. Bakal summarizes what they found:
Dr. Bakal says promising results with immunotherapy have revived interest in using the body’s own inflammatory response to fight cancer, and notes:
“Our study further supports the need to explore the role of inflammation and cancer, in order to enhance treatments and the body’s own ability to eliminate cancer cells.”
Dr. Alan Worsley, senior science information officer at Cancer Research UK – one of the funders of the study – also notes that:
“These results highlight differences between how cancer cells behave in a petri dish compared with in a person, and we need to understand these differences when researching new treatments.”
Funds for the study also came from the Biotechnology and Biological Sciences Research Council and the Wellcome Trust.
Meanwhile, Medical News Today recently learned how researchers designed a copper molecule that shows promise in halting cancer spread. A team of chemists, biochemists and physicists from Bielefeld University in Germany showed that their molecule – which attacks the DNA of cancer cells – killed cancer cells more quickly than the widely used chemotherapy drug cisplatin.