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Cells That Break Down Collagen

December 24, 2013

Fluorescent collagen internalized into the skin cells of a mouse

Fluorescent collagen internalized into the skin cells of a mouse

NIDCR researchers collaborated with an international team of scientists to visualize collagen protein within living tissues and determine which cells degrade it, and they were surprised to find that the most important cell type in animals (mice) was different from the most common cell type identified in previous laboratory (in vitro) studies.

Although many types of cells can make the collagen-destroying enzymes known as collagenases, Thomas Bugge, Ph.D., Chief of the Proteases and Tissue Remodeling Section of NIDCR’s Oral and Pharyngeal Cancer Branch, and colleagues reported in The Journal of Cell Biology that they identified the most important cell type as being a type of blood cell known as an M2-like macrophage. Although one of the usual functions of an M2 macrophage is to clean up cell debris by engulfing and degrading it, in the earlier in vitro studies, fibroblasts—not macrophages—were the cell type that had been most important for collagen internalization and degradation. Their research thus supports the hypothesis that M2 macrophages are involved in tissue repair.

Strong ropes of collagen protein are in skin, bones, tendons, and other tissues. Sometimes it’s normal for collagen to break down, but most times it’s not. An example of undesirable collagen destruction is severe gum disease that leads to the loss of bone and soft tissue that hold teeth in place.  Another example is oral cancer that has the ability to extend from the mouth or throat and invade other parts of the head and neck by degrading the collagen around these healthy tissues.

"What we want to look at next,” said Daniel Madsen, Ph.D., the scientist in Dr. Bugge’s research unit who is lead author of The Journal of Cell Biology article, “is the extensive tissue remodeling process that occurs around tumors.” The team will examine collagen degradation around a tumor to determine whether cancer cells, tumor-associated fibroblasts, or macrophages are most important. Previous studies have suggested that tumor-associated M2 macrophages may promote the growth of cancer and its invasion of nearby tissues.

Dr. Madsen went on to say that, “We speculate that this newly described collagen degrading function of M2 macrophages could contribute to its pro-tumorigenic role. Elucidating the mechanism of collagen degradation in cancer is the first step in devising therapies that could prevent invasion of cancer.”

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This page last updated: March 13, 2014