A Cancer Riddle Solved
University of Iowa researchers reveal
how cancer cells form tumors
By
Richard C. Lewis, University
of Iowa, January 25, 2016
Cancer
is a mysterious disease for many reasons.
Chief among the unknowns are how and why tumors form.
Two University of Iowa studies offer key insights by
recording in real time, and in 3-D, the movements of cancerous human breast
tissue cells. It’s believed to be the
first time cancer cells’ motion and accretion into tumors has been continuously
tracked.
The
team discovered that cancerous cells actively recruit healthy
cells into tumors by extending a cable of sorts to grab their
neighbors—both cancerous and healthy—and reel them in. Moreover, the Iowa researchers report
that as little as five percent of cancerous cells are needed to form the
tumors, a ratio that heretofore had been unknown.
“It’s
not like things sticking to each other,” said David Soll, biology professor at
the UI and corresponding author on the paper, published in the American
Journal of Cancer Research. “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.”
The
findings could lead to a more precise identification of tumorigenic cells
(those that form tumors) and testing which antibodies would be best equipped to
eliminate them. Soll's Monoclonal Antibody Research Institute and the
Developmental Studies Hybridoma Bank, created by the National Institutes of
Health as a national resource, directed by Soll and housed at the UI,
together contain one of the world’s largest collections of antibodies
that could be used for the anti-cancer testing, based on the new findings.
In a
paper published last spring in the journal PLOS One, Soll’s team
showed that only cancerous cells (from a variety of cancers, including
lung, skin, and aggressive brain tumors known as glioblastomas) engaged in
tumor formation by actively soliciting other cells. Like evil-minded
envoys, individual cancer cells extend themselves outward from the original
cluster, probing for other cells in the area, the researchers observed.
Once it detects one, the extended cell latches on and pulls it in, forming
a larger mass. The activity continues, the cancerous extensions drawing in more
and more cells—including healthy cells—as the tumor enlarges.
“There’s
nothing but tumorigenic cells in the bridge (between cells),” Soll
said, “and that’s the discovery. The tumorigenic cells know what they’re
doing. They make tumors.”
The
question is how these cells know what to do. Soll hypothesizes they’re reaching
back to a primitive past, when these cells were programmed to form embryos. If
true, perhaps the cancerous cells—masquerading as embryo-forming cells—recruit
other cells to make tissue that then forms the layered, self-sustaining
architecture needed for a tumor to form and thrive.
Think of
a Death Star that’s built up enough defenses to ward off repeated attacks.
Or, less figuratively, how bacteria can conspire to create an impenetrable film
on surfaces, from orthopedic implants to catheters.
“There
must be a reason,” Soll said. “You might want one big tumor capable of
producing the tissue it needs to form a micro-environment. It’s as if it’s
building its own defenses against the body’s efforts to defeat them.”
In the AJCR paper,
the researchers compared the actions of human breast tissue cells
(MoVi-10') to a weakly tumorigenic, parental breast cancer cell line
(MCF-7). First, they found that over a 50-hour period, MoVi-10'–only cells
grew more in density, primarily by joining together, than did MCF-7.
Also, in
all instances, regardless of the ratio of MCF-7 to MoVi-10' cells in
the cluster, only MoVi-10' cells reached out and drew in other
cells—including healthy cells—to the growing mass.
“The
results 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 authors write.
The
finding lends more weight to the idea that tumors are created concurrently, in
multiple locations, by individual clusters of cells that employ the cancer-cell
cables to draw in more cells and enlarge themselves. Some have argued that
tumors come about more by cellular changes within the masses, known as the
“cancer stem cell theory.”
Soll’s
team also discovered that the Mo-Vi10' cells move at 92 microns per
hour, about twice the speed of healthy cells. That’s
important because it helps scientists better understand how quickly tumors
can be created.
Contributing
authors, all from the University
of Iowa, include Joseph
Ambrose, Michelle Livitz, Deborah Wessels, Spencer Kuhl, Daniel Lusche, and
Edward Voss. Amanda Scherer, now at the University of Michigan, also
contributed to the research while at the UI.