New Targets for Sarcoid Therapy

Ask a roomful of horse people if they've ever seen a sarcoid, and you'll probably see a bunch of hands rise, and many knowing nods or eyerolls of owners who have dealt with these frustrating, usually benign tumors. Sarcoids are the most common skin tumor of equids for which there is currently no universally effective treatment, according to Zhengqiang Yuan, PhD, a research scientist in veterinary pathological sciences at the University of Glasgow's veterinary school in Scotland. Yuan and his research colleagues have made inroads into understanding sarcoids better at the genetic level and identifying novel targets for treating the annoying masses. He described the group's research at the 46th British Equine Veterinary Association (BEVA) Congress, held in Edinburgh, Scotland, in September 2007.

Sarcoids resemble warts, some of which grow very slowly, spontaneously disappear, or are more aggressive and invasive. They can appear anywhere, and all ages and breeds of horses can have them. You're most likely to see sarcoids around the head (in the regions of the ears, eyelids, and mouth), under the belly, and in areas of scar tissue from a wound or surgery.

Yuan noted that it's widely accepted that bovine papillomavirus (BPV), predominantly Type 1, is the main causative agent, but he said little is known about how the horse's cells respond to BPV-1 infection. He and his colleagues compared the gene expression of BPV-1-infected fibroblasts (cells responsible for forming connective tissues)--both experimentally infected cells and those from naturally formed sarcoids--with normal equine fibroblasts (controls).

They found that a subset of genes was modified by BPV-1 in both the experimental and natural sarcoid cells as compared to the controls. These genes with altered expression patterns could be filed under five groups: genes responsible for cellular transformation, apoptosis (cell self-destruction), inflammation and immunity, signaling pathways, and structure. Yuan said this "broad array of biological pathways" will help researchers better understand the disease and further investigate the genes causing it.

"We hope to follow up to find their (the pathways') role in disease," said Yuan. "We can now demonstrate that BPV upregulates MMP-1 expression in vitro and in vivo (in the laboratory and in the live animal)." Matrix metalloproteinases (MMPs) are known destructive enzymes, and they're generally a product for extracellular matrix degradation and are indicative of high collagen turnover. In other words, this "upregulation" or heightened cellular response in the presence of BPV shows us that tissue is undergoing damage at the cellular level.

Yuan described a 3-year study his research group is about to launch. "We think the fact these cells express such high levels of MMPs, this might allow cells to invade surrounding cells, allowing local spread of viral DNA." This might explain why these sarcoids sometimes recur even after surgery for tissue removal, as the damaging cells may have spread, undetected, to the healthy tissue.

About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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