Abstract
A soft, 3D gel made of fibrin may aid in isolating and culturing the cells capable of initiating tumors.
Researchers at the University of Illinois at Urbana/Champaign and the Huazhong University of Science and Technology in Wuhan, China, have developed a method for isolating and culturing the cells capable of initiating tumors, which may prove helpful in studying how cancer spreads.
The experiments in culturing cancer cells, published in Nature Materials, stemmed from earlier work done by Ning Wang, ScD, a professor of mechanical science and engineering at Illinois. Wang had found that embryonic stem cells could be maintained indefinitely in their pluripotent state if grown in a softer substrate than on the rigid plates usually used. Other researchers have shown that some tumorigenic cells may share certain gene-expression characteristics with stem cells.
Theorizing that these cancer cells might prefer a softer, 3D environment just as the embryonic stem cells did, Wang and his colleagues suspended single cells of mouse melanoma in a soft, 3D gel made of fibrin, a fiber-like protein found throughout the body.
After 5 days, the gel cultures contained multiple spherical colonies of cancer cells—many more colonies than grew on plates. The spherical clumping the researchers observed is a typical characteristic of stem cells. The team also found that fibrin-cultured tumor cells expressed the transcription factor Sox2, a stem cell marker.
The scientists injected cells from these colonies into mice, either intravenously or subcutaneously, and found the cells grown in fibrin initiated tumors much more efficiently than cells grown on rigid plates. As few as 10 cells grown in the gel matrix, injected as a clump, induced as many tumors in immune-compromised mice as 10,000 cells taken from a traditional culture. Wang believes this indicates that the fibrin environment also selectively promotes the growth of tumorigenic cells.
Additionally, the fibrin-cultured cells induced tumors in wild-type mice.
Currently, stem cell-like cancer cells are generally isolated via cell surface-marker techniques. Growing the cells in fibrin instead might eliminate the need for labeling or other methods that could alter the cells, Wang says.
