Kleiderer-Pezold Professor of Biochemistry, Director of the W.M. Keck Center for Transgene Research
University of Notre Dame
Frank Castellino and Victoria Ploplis of the W.M. Keck Center for Transgene Research are using mice to study the mechanisms by which components of the hemostasis system regulate the initiation and progression of cancer. Earlier studies have identified a relationship between the regulation of the hemostasis system and tumor growth and metastasis. While it has been shown that elevated levels of proteins of this system are associated with carcinomas of breast, colon, skin, prostate, lung, kidney, and brain, the specific mechanisms by which they contribute to this disease process are still unclear.
By using a colon cancer model in which genetic mutations and deficiencies of hemostasis genes have been introduced in the mouse genome, Keck Center researchers are determining the effects these alterations have on tumor initiation, growth, angiogenesis, and metastasis. Initial studies at the Keck Center have identified urokinase as a major participant in the initial stages of tumor development. Recent studies of the anticoagulant Protein C pathway, have demonstrated that this system may serve as a new therapeutic target for arresting not only ulcerative colitis but also the incidence of colorectal cancer.