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 30?m 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."
