Culture in a Three-dimensional Soft Gel Matrix Promotes Growth of Cancer Stem Cells

Cultivation of a single melanoma cell in a three-dimensional fibrin matrix promoted the development of a spherical colony comprised of highly potent tumorigenic cancer stem cells.

Investigators at the University of Illinois (Urbana, USA) had previously found that stem cells grew better in a soft gel matrix than they did on a rigid plastic plate. Together with colleagues at the Huazhong University of Science and Technology (China) they applied this technology to the culture of melanoma cells.

Results published in the July 1, 2012, online edition of the journal Nature Materials revealed that when cultured within soft fibrin gels, primary human cancer cells, or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumors at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumors in the lungs of wild-type nonsyngeneic mice.

“Starting from single cells, by day five, you have more cells in the soft substrate proliferating,” said contributing author Dr. Ning Wang, professor of mechanical science and engineering at the University of Illinois. “This is exactly the opposite from most cancer cells, which prefer a stiffer substrate. But these cells like to grow in the soft environment. Why is this important? Because they turn into tumors. This may open the door for understanding and blocking metastatic colonization, the most devastating step in cancer progression.”

“Since these cells are more resistant to current cancer-killing drugs than differentiated cancer cells, we would like to see if there are ways to identify and develop new molecules and methods that can specifically target and kill these cells,” said Dr. Wang.

Related Links:
University of Illinois
Huazhong University of Science and Technology