Observing Cancer Cell Behavior
Fluorescence images of pancreatic cancer micro-tumors after overnight culturing. Papillary structures pile up on micro-attachment sites (diameter 30μm), with numerous cells visible per patch. The rightmost micro-tumor has extended over two attachment sites. Nuclei, actin filaments, and microtubules are labeled with blue, green and red fluorescent markers respectively. Credit: Miyatake Y. et al., Scientific Reports, Sept. 19, 2018
A new cell culture platform allows researchers to observe never-before-seen behaviors of live cancer cells under the microscope, leading to explanations of long-known cancer characteristics.
The easy-to-produce platform developed by Hokkaido University researchers offers cancer cells micro-scale attachment sites that elicit never-before-seen behaviors highly relevant to cancer's clinical properties. The observation of these behaviors shed light on the mechanisms behind well-known properties of pancreatic cancer, one of the most lethal malignant tumors, and may lead to the identification of new treatment targets.
"Cancer studies so far either use cell cultures in which cancer cells don't necessarily behave naturally, or tissue samples that don't allow live observation. So there is a big gap in our knowledge of how cancer cells actually behave," says Assistant Professor Yukiko Miyatake, who led the study and focuses on cancer development mechanisms. To close this gap, she teamed up with Associate Professor Kaori Kuribayashi-Shigetomi who specializes on micro-nano-scale bio-engineering.
Together they created a new cell culture substrate from a coated glass slide with etched islands of 30μm diameter. For healthy cells, this is just enough space for one or two to attach. But when the researchers seeded them with pancreatic cancer cells (although they also tried other cancer cells with similar results) and incubated them overnight, the cells self-organized into micro-tumors that could move in a concerted way, as if it were one organism. Precursors to this turned out to be papillary structures that accommodate 4 or more cells by cell-in-cell invasion. This process, called entosis, is so far known only as a step in cell degradation. Here, the incorporated cells remained alive and, to their surprise, the incorporation was reversible.
When they treated the micro-tumors with the widely used anti-cancer agent Nocodazole, the micro-tumor disintegrated, but the now-detached cells survived. Moreover, the researchers observed the micro-tumors "fishing" for surrounding dead cells and ingesting them, in the process releasing chemical markers typical for dead cells. These markers ended up on the cancer cells' surfaces, presumably masking them and enabling them to evade the immune system's killer cells.
Striving to reduce the suffering cancer causes, Miyatake says: "I hope this easy and low-cost technique will find widespread adoption. If the discoveries made during these first observations are physiologically or pathologically relevant phenomena, many more new hints may be gleaned for the development of more effective cancer treatment approaches."
This article has been republished from materials provided by Hokkaido University. Note: material may have been edited for length and content. For further information, please contact the cited source.
Miyatake Y. et al., Visualising the dynamics of live pancreatic microtumours self-organised through cell-in-cell invasion, Scientific Reports, September 19, 2018. doi: 10.1038/s41598-018-32122-w