Pioneering mapping methods aid our understanding of breast cancer cells
The work involved two pioneering methodologies to examine the structure and elasticity of breast cancer cells and the results could now inform future cancer treatments, by furthering our understanding of how the cells are formed and how this affects their movements.
Carried out by experts in biomechanics from the School of Life Sciences at the University of Lincoln and the Istituto Officina dei Materiali (IOM) of the Italian National Research Council in Triestethe, Italy, the study investigated the rigidity of three different lines of breast cancer cells.
The mechanical properties of cells can be measured by their elasticity, which gives an indication of their internal structures. It is already known that cancer cells are sometimes softer and therefore more easily deformed than non-tumour cells, and that this eventually leads to their increased ability to infiltrate tissues and spread from the primary tumour to establish secondary sites. ‘Metastatic’ cancer cells are those that migrate to other parts of the body. The less rigid the cells, the easier it is for them to move away from the original tumour.
This new research informs a body of work examining whether there is a certain threshold of cell structure after which it is more likely for cancer to spread.
Dr Enrico Ferrari, Senior Lecturer in Life Sciences at the University of Lincoln, explained: “In females around the world, breast cancer is the most frequent tumour, and metastasis is in turn the most common cause of complications in breast cancer patients. It is therefore absolutely vital that we, as scientists, gather as much information as possible to inform the treatment of this disease.
“Our research examined three different cancer cell lines, which all had different levels of aggression and metastatic potential. We used two extremely accurate methods to produce thorough characterisations of the mechanical properties of the breast cancer cells, and we hope these will be beneficial in aiding our understanding of the underlying molecular events that lead to metastasis.”
This study primarily looked at the area in the middle of the cell body, which is key to understanding cell elasticity. Much previous research has focussed on the peripheries of the cell as these areas are simpler to analyse, although not as informative.
The researchers used two techniques to measure elasticity at hundreds of points across the cells and produced detailed maps using the results, which are published in the scientific journal Nanotechnology. The first technique is known as Atomic Force Microscopy (AFM), which was conducted in Lincoln, and the second is Optical Tweezer Microscopy (OTM), which was carried out on the same cell lines by researchers in Italy.
Operating on a nano-scale, the AFM method involved probing different points of the cell with an extremely small tip and gently measuring the deformation of the membrane without puncturing it. The measured values were used to create an accurate map of the cell’s rigidity. The minute size of the probe meant that the resulting maps show some of the highest resolutions ever seen in this field of research.
The OTM methodology involved a microsphere made of glass hovering above the surface of the cell, held in place by a laser. As its positioning is manipulated by light, it is an even more gentle method of measuring elasticity.
The researchers combined the results of both methods and as expected, they found that the basal breast cancer cells were softer than their normal counterpart and the less aggressive luminal breast cancer cell line, reflecting their potential to infiltrate other tissues, leading to metastasis.
The techniques used and the conclusions drawn will now contribute to the broader understanding of cancer biomechanics and to the ultimate goal of assessing the potential of cells to lead to metastasis by considering mechanical clues.