W12-005: Immunohistochemical quantification of the transcobalamin II protein (TCII) and receptor (TCII-­‐R) in naturally occurring feline tumors

Cancer affects 4 million cats annually in the United States, and accounts for approximately 32% of disease-­‐related feline deaths. There are only two FDA-­‐approved drugs available for the treatment of cancer in animals and they are labeled exclusively for use in dogs. Current treatment of cancer in cats is based largely on extrapolation from human and canine therapies. Cancer cells rely on vitamin-­‐B12 (cobalamin) for cell growth. Cancer cells produce transport proteins to scavenge vitamin-­‐B12, and they express more vitamin-­‐B12 receptors on their surface than healthy cells.

Current research is focusing on the use of vitamin-­‐B12 in tumor imaging as well as anti-­‐tumor therapy. Nitrosylcobalamin (NO-­‐Cbl), an anti-­‐tumor drug, uses vitamin-­‐B12 to target cancer cells where the vitamin-­‐B12 is bound to nitric oxide. Nitric oxide is toxic to cancer cells. NO-­‐Cbl is bound to transport proteins and carried to the receptors on the cancer cells, delivering a toxic nitric oxide payload. Toxicity to other cells is avoided since cancer cells express more vitamin-­‐B12 receptors than normal cells and nitric oxide release occurs only inside the cells. Vitamin-­‐B12 transport protein and receptor expression has never been studied in feline tumors. The purpose of this study is to quantify this protein and receptor expression in feline tumors using immunohistochemical staining. Results from this study will be used to identify feline tumors susceptible to vitamin-­‐B12-­‐ based imaging and treatment with drugs such as NO-­‐Cbl.

Grant ID: W12-005

Status: Active

Year Funded: 2012

Amount awarded: $17,663

Investigator: Annette M. Sysel, DVM, MS; Joseph A. Bauer, PhD; Bauer Research Foundation, Akron OH