Insight

Fall 2004

Unique Retroviral Tumor Offers Clues to Natural Cancer Regression

Walleye are most often thought of as a sport fish, but to cancer researchers at Colorado State University the fish is a great catch for the opportunities it offers to study a rarity in the world of cancer – naturally regressing tumors.

Dr. Sandra Quackenbush and her research team, graduate student Tina Daniels and special appointment faculty Dr. Joel Rovnak, recently arrived at Colorado State – by way of the University of Kansas – where they are continuing walleye studies originated at Cornell University. The team is studying the properties of a retrovirus that causes “stop-and-go” dermal sarcomas in the walleye.

“The natural biology of the disease is somewhat unique in the world of cancer research,” said Dr. Quackenbush, an Assistant Professor in the Department of Microbiology, Immunology and Pathology. “In the fall, the tumors first appear on the fish, popping up all over their bodies. The tumors grow through the winter and are at their peak in the spring when the walleye are spawning. This is also when the tumors are shedding substantial quantities of virus, quite understandable because the virus is spread through contact. After spawning, the tumors begin to regress, eventually falling off and leaving the fish perfectly normal. Come fall, the cycle starts again.”

Studying fish obtained from a hatchery on Oneida Lake, Syracuse, New York, where there is a high incidence of the disease, Dr. Quackenbush and Drs. Jim Casey and Paul Bowser of Cornell started working on a system to better understand the mechanisms of the retrovirus and what proteins might be causing the growth and regression of the dermal sarcomas, as well as to investigate fish tumor retroviruses as new models for oncogenesis (the formation and development of tumors).

“We have three goals in our current research,” said Dr. Quackenbush. “We want to understand what viral proteins are responsible for oncogenesis, what viral proteins are associated with the regression of tumors, and how virus expression is regulated. What we do know is that around the time of spawning, something happens and we see a tremendous increase in viral gene expression. We want to learn more about that trigger.”

To date, researchers have been able to reproduce the disease experimentally, but have not been able to replicate conditions for regression. They also have discovered that the virus encodes three novel proteins with functions that are uncertain. But Dr. Quackenbush and her team do have some theories. The first viral protein in the developing tumor seems to inhibit viral gene expression and also seems to affect cellular gene transcription. The second protein is expressed in the developing tumor and seems to be involved in cell signaling, most likely with oncogenesis. The third protein, and one of the most interesting, is expressed in the regressing tumor so is likely to be a key factor in tumor regression and also may be involved in up-regulating virus transcription associated with cells that will undergo apotosis (programmed cell death).

In another fish cancer study, Dr. Quackenbush is investigating swim bladder sarcomas in Atlantic salmon. These tumors also are caused by a retrovirus, but the tumors do not regress and can be a significant problem for the salmon industry. Though the walleye is the significant portion of the laboratory’s focus, Dr. Quackenbush believes there is much to be gained from knowledge acquired in both projects.

“We believe there is much to be learned by medical science in the development of these fish models as relates to cancer research,” said Dr. Quackenbush. “In the future, it will be quite interesting to see where our studies lead us.”

Dr. Quackenbush and her research team are supported in the walleye studies by a grant from the American Cancer Society. Work in the Atlantic salmon is supported with funding from the United States Department of Agriculture.