Metastasis is the major cause of death in cancer patients due to cancer cell dissemination to distant organs. Cell plasticity is a core characteristic of metastatic cells and tumour aggressiveness.
The PLAST_CELL project aims to quantify a cancer cell’s ability to respond to environmental stress that threatens its survival, a key indicator of tumour progression and aggressiveness. The initiative, funded by the European Innovation Council, brings together researchers from five organisations, including EMBL’s European Bioinformatics Institute (EMBL-EBI).
In response to changing environments that threaten their survival, cancer cells have an extraordinary ability to change their behaviour, shape and function. This trait, a key indicator of tumour progression and aggressiveness also known as cell plasticity, allows cancer cells to adapt to stress and keep growing.
Cell plasticity is fundamental for cancer’s ability to cheat death. For example, cells can switch to using old and damaged parts to keep functioning or activate cellular programs that freeze them in a state of senescence. Cells can also detach from a primary tumour and invade other tissues, contributing to metastasis, even with the body normally inducing cells to self-destruct in the absence of proper cell-to-cell interactions.
Despite playing a central role in cancer progression, there is no universal consensus on the definition of cell plasticity. Being able to quantify the impact of these mechanisms would be a huge boon for cancer research and treatment, paving the way for new tools that predict how aggressive a tumour is and, at the same time, boost the development of more effective and personalised cancer therapies.
“When cancer cells attempt to relocate to a new part of the body to metastasise, they have to overcome a series of challenges. It’s like a decathlon at cellular scale, but instead of swimming, running or jumping, cancer cells have to physically squeeze through spaces, adapt to different chemical and physical environments or interact with new types of cells when changing locations in the body. If we could quantify the cellular ‘fitness’ in these events like in a scoring system used in sports, we could predict tumour aggressiveness and metastatic potential,” says ICREA Research Professor Verena Ruprecht, researcher at the Centre for Genomic Regulation (CRG) in Barcelona, who is leading the consortium.
PLAST_CELL aims to develop a technology that will mimic the physiological stresses that naturally occur in the human body and provide quantitative readouts on a cell’s shape, proliferation and survival and molecular features associated to its capacity to adapt to different environments.
“We will create a high-resolution live-imaging microscope which will be connected to a device that can mimic the stress that cancer cells face when proliferating and colonising different organs, including the mechanical ‘squeezing’ of cells in dense tissues or during migration” explains Ruprecht. “With this information, we can study cancer cells with known low or high metastatic potential. The images result in the creation of datasets that will feed AI tools and ultimately help predict the metastatic potential of cancer samples from patients.”
The live-imaging microscope will be used to set quantitative standards to identify genetic, molecular, and biophysical mechanisms underlying cancer cell plasticity and tumour aggressiveness. The consortium believes the platform will give rise to ‘Plastomics’, an entirely new field in biology which can provide a new perspective in cancer analysis, diagnosis and – in the future – treatments.
The researchers anticipate that pharmaceutical drug discoveries targeting metastatic potential and resistances will emerge based on PLAST_CELL within a ten-year period. The platform also aims to be adopted in the clinic as a new and powerful diagnostic tool to assess tumour aggressiveness.
“EMBL-EBI is contributing expertise in image processing and computer science to this exciting initiative,” explains Virginie Uhlmann, Research Group Leader and Deputy Head of Research at EMBL-EBI. “We’re hoping to reconcile what happens in 3D in the real world, and what we capture in 2D images using microscopes. My group helps to address this challenge by developing automated microscopy image quantification algorithms, blending mathematical models and machine learning with a focus on computational morphometry, which is the study of shape variation. ”
This project is a collaboration between the Centre for Genomic Regulation (CRG), Institut Hospital del Mar d’Investigacions Mediques (IMIM), ICFO, EMBL-EBI and French SME Cherry Biotech.
This project has received funding from the European Union’s HORIZON-EIC-2021-PATHFINDEROPEN programme under grant agreement No 101046620.
This announcement was originally published on the PLAST_CELL website.
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