USC News

Menu Search

USC researchers show how collagen inhibits cancer

The body’s connective tissues—and, in particular, the fibrils of collagen that make up those tissues—are able to directly inhibit the growth of cancer cells through the activation of a tyrosine kinase receptor on the surface of those cells.

A team led by Steven Wall and Yves DeClerck from the Saban Research Institute of Childrens Hospital Los Angeles and the Keck School of Medicine, along with colleagues from Emory University in Atlanta and the University of California, San Francisco, published their findings in the Dec. 2 issue of the Journal of Biological Chemistry.

Previous research had shown that collagen can and does inhibit the spread of cancer cells, but had been unclear as to whether that inhibition came from a sort of physical barrier created by the collagen that stopped the cells from infiltrating the tissue, or from some more direct mechanism that impedes cell growth.

“The presence of collagen fibers in the tissue penetrated by malignant cells is a physical barrier against their invasive behavior,” the researchers wrote. “However it has been suggested that collagen fibers also restrict cell proliferation.”

To assess whether that suggestion had any scientific basis, DeClerck and colleagues examined the in vitro growth of human melanoma cells in the presence of collagen and found that, as expected, they stopped growing in the early phase of the cell cycle. But when they studied the results of interference with a key surface receptor for the signaling protein tyrosine kinase—a receptor that, when activated, binds to collagen—they saw a change in these patterns. When the receptor in question—called the discoidin domain receptor 2—was inactivated through the use of the typrosine kinase inhibitor genistein, or the downregulation of the receptor itself, or the prevention of receptor activation, the melanoma cells continued to grow and cycle unabated.

Thus, under normal in vivo conditions, the fibers of collagen found in connective tissues work to prevent melanoma cells—and probably other cancer cells—from spreading through the tissue through two mechanisms: They physically block the spread of the cells and, simultaneously, activate the tyrosine kinase receptors on those cells’ surfaces to signal an end to the cell’s growth cycle.

Obviously, collagen is not all-powerful; the cancer cells, in response to this two-pronged attack by the fibrils, secrete chemicals that act to denature and destroy the collagen fibrils, knocking out both of the connective tissue defenses with a single blow.

“In summary, our observations provide evidence for the existence of a direct, cell receptor-mediated mechanism by which the [extracellular matrix] controls the proliferation of malignant cells that…is independent of cell spreading and cytoskeletal organization,” the scientists noted. “They also confirm that degradation of [fibrillar collagen] by invading tumor cells in addition to providing a mechanism to remove a physical barrier is an important way to escape growth-limiting signals.”

This study was supported by grants from the National Cancer Institute.

Steven J. Wall, Erica Werner, Zena Werb, Yves A. DeClerck, “Discoidin Domain Receptor 2 Mediates Tumor Cell Cycle Arrest Induced by Fibrillar Collagen.” Journal of Biological Chemistry, Dec. 2, 2005.

USC researchers show how collagen inhibits cancer

Top stories on USC News