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Lady and the Tramp

Mouse models of prostate cancer point to new targets for imaging, treatment

June 22, 2011 | Leigh MacMillan

Sitting next to the biology and medical tomes on a shelf in Robert Matusik’s office are two stuffed animals: Lady and the Tramp. They are there in homage to the mouse models of prostate cancer – fondly called lady and tramp models – that Matusik and his colleagues have generated.

“We are all waiting for Disney to sue us,” laughs Matusik, Ph.D., professor of Urologic Surgery, Cancer Biology, and Cell & Developmental Biology at Vanderbilt University.

Robert Matusik, Ph.D.

"Lady" and "tramp" are helping Robert Matusik, Ph.D., and colleagues study the how prostate cancer develops. (Photo by Joe Howell)

Tramp was the moniker applied to the first mouse model of prostate cancer, sometime after the 1995 publication that described the new model; Matusik was an author on the paper. (Tramp stands for transgenic animal model for prostate cancer.)

“We went on to develop some different models in my laboratory, and I got kind of tired of everyone saying we worked on tramp mice, so we nicknamed some of our new models ‘lady,’” Matusik explains. (Lady doesn’t stand for anything, but Matusik notes that his group’s models always get first billing – “You never say tramp and lady.”)

“My biggest contribution to science is the piece of DNA we characterized” that allows investigators to target genes to the prostate, he says.

“This really opened up the field of making mouse models for prostate cancer,” he adds, noting that he continues to supply this tool to researchers who request it and that more than 400 laboratories worldwide have used it to date.

Mouse models allow investigators to follow the development of prostate cancer – from an early pre-cancerous lesion to a deadly metastatic disease. Using mouse models, Matusik and others have characterized critical molecular pathways that contribute to tumorigenesis and that offer new therapeutic targets. Mouse models also can be used to test the effectiveness of new therapies for treating – and for preventing – prostate cancer.

Using mouse models, Matusik and his colleagues have learned that as prostate cancer advances, some of the cells take on “neuroendocrine” features. The researchers showed that the neuroendocrine-differentiated cells secrete growth factors that promote tumor growth, even in mice without testosterone.

These mice offer a tool for finding ways to treat advanced prostate cancer that begins to grow after androgen deprivation (hormone) therapy.

In collaboration with Ronald Walker, M.D., and Eric Liu, M.D., at Vanderbilt, Matusik is developing compounds based on the neuroendocrine features that they hope will be dually useful for advanced prostate cancer – for imaging and for therapy. The investigators’ first goal is to develop imaging compounds to follow advanced prostate cancers to assess whether or not treatments are working. They also hope to use the compounds as transport vehicles to selectively deliver a killing dose of radiation to the tumor.