Real-time, 3D recordings of cell behavior show how tumor-forming cells draw in other cells by extending cellular cables and forming bridges to other clusters.
Image credit: Soll Laboratory/University of Iowa.
The study - by the University of Iowa (UI) - is published in the American Journal of Cancer Research and describes how the scientists came to their conclusions by studying 3D recordings in real time of the movements of cancerous human breast tissue cells.
They found that a small group of tumorigenic cells - cells that form tumors - extends a sort of cellular cable to grab neighboring cells - both healthy and cancerous - and reel them in to create and enlarge the tumor mass.
The finding may help explain why tumors contain such a large proportion of healthy as well as cancerous cells.
Senior and corresponding author David Soll, a UI biology professor, explains how what they saw made them realize the process is not just a case of cells simply sticking to each other:
"It's that these cells go out and actively recruit. It's complicated stuff, and it's not passive. No one had a clue that there were specialized cells in this process, and that it's a small number that pulls all the rest in."
Only 5% tumor-forming cells needed to start a tumor
In previous work, the team had shown - using cells from a variety of cancers - that only cancer cells have a propensity to form tumors by actively soliciting other cells.
They discovered that individual cancer cells extend themselves outward from the original cluster and probe for other cells in the vicinity. As the process ensues, the tumor grows as the cancer cells draw in more and more cells.
In the new study, the team shows how only as little as 5% tumorigenic cells can actively pursue tumor formation and get cancerous and healthy cells to clump together by forming cellular cables between them. This is the first time such a ratio has been discovered.
The tumor mass thus grows as a structure made of lots of cells joined together by bridges where the cables extended to draw in cells, as Prof. Soll explains:
"There's nothing but tumorigenic cells in the bridge (between cells), and that's the discovery. The tumorigenic cells know what they're doing. They make tumors."
There still remains the question of how the tumorigenic cells know what to do. Prof. Soll speculates they are reaching back to a primitive program that is active during embryo development.
Regardless of ratio, only tumor-forming cells draw in other cells
For their study, the team worked with three human breast cell lines. One is known to be tumor-generating or tumorigenic and is called MoVi-10'. Another cell line, called MCF-7, is weakly tumorigenic, and the third, MCF-10A, is non-tumorigenic.
The researchers notice how, regardless of the ratio, only MoVi-10' cells reached out and drew in other cells - including non-tumorigenic cells - to the growing mass.
They also describe how they found that even if only 5% of the cells are MoVi-10' they "will actively cause primary aggregates of majority MCF-7 cells or MCF-10A cells, formed by cell multiplication, to undergo coalescence."
The authors conclude:
"The results presented here extend our original observation that tumorigenic cell lines and fresh tumor cells possess the unique capacity to undergo coalescence through the active formation of cellular cables."
The finding supports the idea that tumors form in different locations at the same time, as a result of individual clusters of cancer cells that enlarge themselves using cellular cables to pull in more cells.
The team also found that the Mo-Vi10' cells move at 92 microns per hour, much faster than healthy cells, which can only move at half this speed. This detail is important because it helps us better understand the speed at which tumors can form.
The researchers hope the study will lead to better ways of identifying tumorigenic cells and finding antibodies that target them.
Meanwhile, Medical News Today recently learned of another study that suggests the development of cancer might be predicted using a mathematical model based on patterns of natural laws. The researchers foresee the model using genetic data extracted from tumors to predict how a given cancer will develop over time and thus help doctors decide how best to treat it.