U of M researchers find multifunctional protein may slow progress of head and neck cancer

U of M researchers find multifunctional protein may slow progress of head and neck cancer

Breakthrough

A collaborative study led by researchers from the Masonic Cancer Center, University of Minnesota and the University of Minnesota School of Dentistry, has discovered that the multifunctional protein complex calprotectin, found inside cells, may be used to slow the growth of head and neck cancer.

The growth rate of normal cells is tightly controlled by multiple cell cycle checkpoints that slow down and regulate cell growth. But when a cell becomes cancerous, one or more of its cell cycle checkpoints become damaged and the cell loses the ability to control how fast it grows. The damaged cell rapidly divides to form a life-threatening tumor.

For years, scientists have speculated that the apparatus controlling the cell cycle checkpoint included the proteins S100A8/A9, which make up the protein complex calprotectin, but there was little direct evidence.

In head and neck cancer tissues, the amount of calprotectin is typically reduced to levels less than in normal cells. The U of M researchers hypothesized that in head and neck cancer, the loss of calprotectin causes abnormal cell growth because of a loss of cell cycle checkpoint control.

The latest research, conducted largely by Ali Khammanivong, M.S., Ph.D., a researcher from Masonic Cancer Center, University of Minnesota, specializing in Comparative Oncology and Veterinary Clinical Sciences researcher, is published today in the journal PLoS ONE.

School of Dentistry researchers who co-authored the study include Principal Investigator and senior author Mark Herzberg, D.D.S., Ph.D., Brent Sorenson, M.S., Karen Ross, Ph.D. and deceased postdoctoral fellow Chengxing Wang, D.D.S., Ph.D.

“We learned that calprotectin works as a brake - similar to a brake in a car - to regulate the cell cycle and growth,” explained Herzberg. “When an epithelial cell is cancerous, it makes less calprotectin. Our findings suggest strongly that the loss of calprotectin causes the cancer to grow faster because, figuratively, the foot is off the brake.”

Researchers found that reintroducing calprotectin back into the cancer cells or reactivating molecular pathways controlled by calprotectin may help reduce tumor formation and progression.

What could this mean?

“Since the loss of calprotectin production and function is commonly found in head and neck cancer, our results might also provide a means for detecting potential cancerous growth as well as new treatment strategies for head and neck cancer,” said Khammanivong. “Similar mechanisms may also present in esophagus and cervical cancers, where the tumors emerge from similar types of mucosal tissues.”

Although these tests have yet to be conducted in animals, the lab results are promising. Khammanivong and his colleagues are hopeful that one day their results will translate into new treatment options for an otherwise unforgiving disease.

“Often head and neck cancer is at a late stage when diagnosed and normally doesn’t respond sufficiently well to radiation or chemotherapy. Whereas the prognosis of cancers of different tissues in the head and neck can vary widely, patients on average have a survival rate of five years,” said Herzberg. “Those patients who do survive are often left coping with disfigurement from surgery and psychological trauma. Perhaps what we have learned can lead to a less invasive way to treat head and neck cancer.”

Study background

Wang began the research as a postdoc in Herzberg’s lab. After investing almost a year in the work, he was diagnosed with clear cell carcinoma, a cancer of the lung, and was given less than six months to live.

While being treated at the Masonic Cancer Center, University of Minnesota, Wang passed on his project to Khammanivong, who was a Ph.D. student in the Graduate Program in Oral Biology studying in the Herzberg lab. Wang continued to work on the research in the School of Dentistry and lived a year longer than expected. His colleagues were able to help see his research through to publication. This project was supported by a grant from NIH/NIDCR.

Khammanivong is currently a postdoctoral fellow in the laboratory of Erin Dickerson, Ph.D. at the Masonic Cancer Research Center.

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  • Last modified on August 13, 2013