Once upon a time, there were three metastatic cancer cells looking for a new home. They floated and floated through their host body, each looking for a suitable place to build a new tumor.
The first landed on the heart—a strong, stiff, muscular tissue. It thought, “Oh dear, this is much too uncomfortable for me to build on.” So it went dormant and did not build its tumor.
The second landed on the surface of a femur—a long, strong, stiff bone. It thought, “Oh dear, this will never do. My surrounding are much too uncomfortable to build on.” So it went dormant and did not build a tumor.
The third tumor, however, landed on a lung—a nice, soft, squishy organ if there ever was one. “This is perfect,” it thought. “I shall build a giant, strong tumor to call my own.”
And it did.
Fairy tale? Yes. Complete fiction? No. At least, not according to new research from the University of Illinois.
Ning Wang, the Leonard C. and Mary Lou Hoeft Professor in Engineering and professor of mechanical science and engineering, led a team of researchers in a study looking at what characteristics determine whether or not a dormant but spreadable cancer cell develops into a new tissue.
Thanks to advances two years ago allowing the group to select tumor-repopulating cells from a culture, the researchers isolated such cells from melanoma, an aggressive skin cancer notorious for spreading and recurring. They grew these repopulating cancer cells on gels of different stiffnesses—as you might have guessed by now, some were soft and some were stiff to mimic different types of body tissues.
The cells placed in very soft gels grew and multiplied, as expected. The cells placed on stiffer gels did not proliferate—they became dormant. When the researchers later transferred them to a soft gel, the cells “woke up” and began to multiply and spread.
Wang speculates that these properties of dormancy and reawakening when the mechanical environment is more inviting may explain why soft tissues, such as the brain or lungs, are most vulnerable to metastasis.
“We have many different types of organs where solid tumors originate, but if you look at the metastasized sites, the majority are in soft tissues,” said Wang. “Brain, lung, liver and bone marrow, all soft. So it may not be coincidence. We need to do more research.”
What’s impressive to me about this is the ability to grow and pluck out the cancer cells that become dormant—that’s a huge deal. There is a very low percentage of these types of cells in any given tumor, and figuring out what makes them different from their peers would be a huge step toward finding a way of stopping their spread.
I had no idea they could do that.
The paper, “Matrix softness regulates plasticity of tumor-repopulating cells via H3K9 demethylation and Sox2 expression,” was published in Nature Communications by Wang and no fewer than 23 coauthors—that’s an et al if I ever saw one.