Metastasis is cancer’s deadliest weapon. Now, scientists have caught it in the act—watching tumor cell clusters invade blood vessels in real-time, revealing a surprising biological strategy for spreading through the body.
Key Points at a Glance
- Tumor cell clusters are far more likely than single cells to cause metastases
- Researchers observed clusters dismantling blood vessel walls to enter the bloodstream
- High TGF-β and activin levels trigger endothelial-to-mesenchymal transition in vessels
- A new 3D vessel-organoid system enabled real-time tracking of invasion
- Study may lead to therapies that prevent metastatic spread by targeting vessel infiltration
For years, scientists have known that clusters of circulating tumor cells—tiny gangs of cancer—are much more dangerous than lone cancer cells. But exactly how these clusters breach blood vessels to travel through the body has remained a mystery. Now, researchers from The University of Tokyo and several Japanese institutions have observed this moment with unprecedented clarity.
In a study published in iScience, the team created a groundbreaking 3D culture system that mimics human tissue, complete with artificial blood vessels and intestinal tumor organoids. Using advanced live-imaging, they watched tumor clusters migrate toward blood vessels, force their way in, and disperse once inside the bloodstream—exactly the behavior that enables metastasis.
“Clinical data told us these clusters were key to metastasis,” said Professor Yukiko Matsunaga, senior author of the study. “But we didn’t know how they crossed the robust barrier of the blood vessel wall. Now, we’ve seen it happen.”
The breakthrough lies in the biology. As tumor clusters approach, they trigger high expression of transforming growth factor-β (TGF-β) and activin in the endothelial cells that line the vessel wall. These molecules spark a process called endothelial-to-mesenchymal transition, or EMT, where parts of the vessel wall lose their structure—just enough to let the tumor cells through.
“We saw the blood vessel wall being partially dismantled in response to the approaching cluster,” said Dr. Yukinori Ikeda, co-lead author. “It’s like the vessel is being convinced to open the door.”
Once inside, the cluster disperses, seeding the bloodstream with cells that can lodge in distant organs and create new tumors. For patients, this is where cancer becomes lethal.
The new 3D model—dubbed a “tumor-microvessel on-a-chip”—not only captures the mechanics of this infiltration, but opens a path to studying and eventually disrupting it. It’s a precision tool for decoding metastasis.
“Our system gives researchers the power to develop treatments that specifically prevent blood-vessel invasion,” said co-author Dr. Makoto Kondo. “If we can stop the cluster from entering circulation, we could drastically improve outcomes in late-stage cancer.”
With metastasis responsible for the vast majority of cancer-related deaths, this discovery could shift the paradigm of cancer treatment from chasing tumors to barricading the blood highways they use to escape.
Source: The University of Tokyo – Institute of Industrial Science
