Cancer cells form ‘teams’ to help incurable childhood brain tumors spread
Scientists reveal how different cancer cells form ‘teams’ to help childhood brain tumors spread
Human DIPG cells (orange) grown on mouse brain ‘slices’ (light blue), treated with the drug combination, trametinib, and dasatinib and show dying cells in the middle.
Scientists have shed light on how different types of cancer cells interact and work together to spread aggressive childhood brain cancer.
Using mathematical modeling, the team provides a framework for detecting, measuring, and mapping interactions between different types of cells in diffuse intrinsic pontine glioma (DIPG) – a brain tumor that begins in a type of cell known as ‘ known as ‘immature glial progenitor cells’. other parts of the brain.
Researchers from The Institute of Cancer Research, London, led the study published in Cell Reports. cancer cells
They hope that targeting and blocking the interactions that allow cells to work together to invade surrounding areas could become a new treatment strategy, which is urgently needed in currently incurable childhood cancers.
Cancer Cells cooperate within the tumor
DIPG tumors are composed of more than one subtype of the cancer cell. In 2018, a team of scientists from The Institute of Cancer Research (ICR) found the first evidence that different subtypes of cells within a tumor can cooperate – rather than outright compete for resources, as was commonly believed.
Their new findings show for the first time that some subtypes have a positive effect on others in how cells spread – opening new avenues for testing and treating this childhood cancer.
The study, funded by Cancer Research UK, explored the interplay between two different subtypes of cancer cells – labeled VI-E6 and VI-D10 – that when grown together in the laboratory, were derived from tissue donated from patient biopsies. have gotten. The VI-E6 subtype was able to proliferate further when grown in co-culture with VI-D10.
Collaboration more than doubled the spread
Using deep learning to process images from experiments in the lab, the scientists were able to identify interactions where one cell subtype cooperated and helped another to grow and spread – and map these interactions and those of others. Where one subtype spreads more than the other due to other unrelated factors, such as space restrictions.
Previous models exploring cooperation between cancer cells focused on growth, but this innovative study is the first to measure the interactions that affect the way tumor cells spread and invade surrounding areas.
The researchers demonstrated that cells behave differently when cultured together in the laboratory, rather than in separate environments. Culturing the two different subtypes together resulted in a twofold increase in tumor proliferation.
When they grew the two different cell subtypes together, the researchers found that the cancer cells were able to spread and invade a larger area. While one subtype travels and spreads more quickly, the speed of the other is reduced – highlighting commensal interactions, where one subtype gains benefits without harming the other, as well as exploitative interactions, where fitness is reduced. The fitness of a subtype is increased by doing Of the exploited subtype.
The findings suggest that interactions between DIPG cell subtypes play an important role in helping tumors to invade and spread through the local environment – adding to our understanding of how childhood cancer progresses.
In this way, the researchers provide a framework that can be applied to more types of cancer. By providing a method to identify and measure these cell interactions the effect of the treatment can also be ascertained.
Researchers are becoming increasingly aware of the importance of differences between cancer cells within the same tumor, which can have an effect on treatment outcomes. Their hope is that identifying and measuring interactions between cancer cell subtypes could lead to better and more personalized treatment options.
The study was co-led by Professor Chris Jones and Professor Andrea Satoriva, former Center for Evolution and Cancer team leader at the ICR.
Attacking tumors by ‘disrupting the positive conversation’
Study co-leader Professor Chris Jones, Professor of Childhood Brain Tumor Biology at The Institute of Cancer Research, London, said:
“This childhood cancer is incredibly difficult to treat. Nearly all children with DIPG die within two years, and new treatments are urgently needed.
“We are just beginning to understand how the different types of cells in DIPG interact and work with each other to promote disease.
“By combining deep learning and advanced mathematical modeling with experimental data, we provide a framework to detect, measure and map these interactions – which we expect can lead to tumor growth by inhibiting positive interactions and promoting negative interactions.” attacking
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‘Stopping cancer in its tracks
Study author Dr. Haidar Tari, who was part of the evolutionary genomics and modeling team at the Institute of Cancer Research, London, said:
“If one subtype cooperates with a different subtype that drives tumor growth and spread, then targeting and blocking this cooperation will be important – with the goal of stopping cancer in its tracks.
“This innovative study provides a way to identify where cells are interacting and by how much, and the framework can be applied to a variety of cancers.”
‘Discovering research brings hope’
Dr. Laura Danielson, Children’s and Young People’s Research Lead at Cancer Research UK, said:
“More work is needed to understand how we can potentially target these interactions, but exploratory research like this brings hope for developing more effective treatments for children and young people affected by cancer.” “