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A new method of 3D culture precisely quantifies how cancer cells generate spreading forces in tissues

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Research to understand how cancer grows and metastasizes has traditionally been done in two-dimensional flat cell cultures, which differ greatly from the conformation of cells in the body. His 3D cell cultures incorporating tissue material were developed, but there was no way to measure how cancer cells use force to spread.

Researchers have now developed a new method of 3D culture to precisely quantify how cancer cells generate spreading forces within tissues. “We applied this method to investigate the early progression of breast cancer,” said Juho Pokki, a principal investigator at Aalto University who led the study.

The study, a collaboration of scientists from Aalto University and Stanford University, was published in the journal. nanoletter.

Nanospheres measure pulses of force that build up into stronger forces

A primary tumor may form in the ducts of the breast, where cancer cells are enclosed by a special membrane called the basement membrane. Breast cancer cells are larger than the pores in these membranes and must break through to spread to other tissues. It was previously thought that cells use enzymes to dissolve membranes, but it is now understood that breast cancer cells use a different mechanism to cross membranes, including cell protrusions.

“In this mechanism, breast cancer cells use forces generated by protrusions to open channels within the membrane material. Cancer cells then enter the surrounding tissue and further migrate into blood vessels to the rest of the body.” “In fact, blood vessels are also surrounded by basement membranes. Breast cancer cells may use similar mechanisms to invade these basement membranes,” Pocki explains. “Professor Ovijit Chaudhuri’s group at Stanford University first discovered this protrusion mechanism in 2018. Working with his group is key to the physiological implications of this study,” said Pokki. says.

A new study uses 3D cell cultures composed of breast cancer cells and standard basement membrane materials. The researchers implanted two of his biocompatible spheres within her 3D culture. Using a modified fluorescence microscope, we captured videos of these spheres and tracked them at the nanoscale.

This allowed researchers to measure force pulses from cancer cells. “Previous studies have measured the movement of cell processes over long periods of time, but our study showed that a lot can happen in just 15 minutes. “We’ve seen nanoscale motion and force pulses within, which is surprising. What’s more, these pulses accumulate, increasing the force exerted on the membrane material,” says Pocki.

“This is currently the most accurate method for measuring how cell forces are generated in 3D culture,” adds Pokki.

Towards more efficient and personalized drug development

Breast cancer is the most common form of cancer for women worldwide. Each year, more than 350,000 women in the European Union alone are diagnosed with breast cancer.

Developing therapeutics for breast cancer is costly, time-consuming and often inefficient. Less than 5% of his drug candidates, selected using 2D cell culture and animal studies, have proven effective in human clinical trials.

“Our method provides more accurate computational data on cell forces during invasion by breast cancer cells. increasing reproducibility.I believe that the development of technology will eventually boost preclinical research.We have already started related projects in the area of ​​personalized cancer care. ‘, Pokki reveals.

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Journal reference:

https://doi.org/10.1021/acs.nanolett.2c01327

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