The study, which represents an advancement in single-cell imaging techniques, has recently been published in the journal Cell Reports.
Single-cell imaging refers to the set of microscopy techniques used to collect data from individual cells instead of averaging the values of populations of cells. Single-cell imaging usually involves fluorescent molecules.
For the new research, Japan-based scientists combined the existing single-imaging techniques with a new chemical mixture. The so-called clear unobstructed brain/body imaging cocktail (CUBIC) enabled them to see cancer cells multiply and spread throughout the bodies of mice.
The innovative imaging protocol made the mice's bodies, right down to their organs, markedly transparent. This technique is significant because it provides a much clearer understanding of the metastatic process while unraveling some of its steps, many of which have been a mystery until now.
Additionally, as the authors explain, the research brings us closer to "one of the ultimate goals in biology and medicine," which is a "comprehensive analysis and decoding of the more than 100 billion cells comprising the mammalian body."
Using CUBIC to view cancer cells
Showing what happens to individual cells during metastasis was no easy task. During metastasis, cancer cells not only spread within the same organs - by moving into healthy tissue nearby - but they can also travel to more distant locations within the body.
During the imaging process, in order to locate the cancer cells, researchers must pick up the signals from the fluorescent molecules. However, they also have to make sure that these signals are preserved when the tissues are made more transparent using methods such as "tissue-clearing-based 3D imaging."
This is why the researchers used CUBIC - a method that they formerly developed for whole-body imaging of mice that were 1 day old - and optimized it so that it could identify cancer cells.
The refractive index optimization enabled the researchers to make the organs highly transparent while still preserving the fluorescence signals. This allowed the team to find and view cancer cells spread within organs such as the liver, pancreas, lungs, and intestines.
The video below shows whole-brain imaging of the metastasis process:
The protocol has already provided valuable insights. For instance, it became visibly clear that cancer cells must "surf" the bloodstream, going in and out through the walls of the blood vessels in order to reach other parts of the body.
"Most cancer cells are not so lucky and die during the trip," explains corresponding study author Kohei Miyazono, of the University of Tokyo.
"But," he adds, "images obtained through the new method suggest that cells treated with TGF-beta, a protein that regulates cellular growth and differentiation in humans and is produced in increased quantities by some cancers, are far more likely to survive the journey and form malignant outposts."
"The study demonstrates the power of whole-body and whole-organ clearing and imaging with single-cell resolution [...] We believe that same strategy will be applicable to other biomedical studies such as autoimmunity and regenerative medicine, in which the single-cell events play crucial roles."