Baker Institute for Animal Health
Email: email@example.com; Phone: 607-256-5624
Sponsor: Morris Animal Foundation
Grant Number: D14CA-063
Title: The Role of Citrullination in Canine Cancer Stem Cells: Opportunities for Novel Anti-tumor Strategies and Biomaker Development
Project Amount: $50,001
Project Period: 09/01/13-08/30/14
DESCRIPTION (Provided by Applicant): The peptidylarginine deiminases (PAD) are a family of calcium-dependent enzymes that citrullinate proteins. PAD activity appears to be quite low in normal tissues but often increases dramatically during disease progression such as cancer. We and others recently found that PAD2 and PAD4 are strongly up-regulated in tumor-initiating epithelial cells from the mammary gland. These cells, also named cancer stem cells (CSC), represent a small subset of cells within tumors that are believed to be responsible for tumor initiation, growth and metastasis. Further, we have found that PAD inhibitors potently block tumor progression in mouse models of human breast cancer. Together, these findings raise the intriguing possibility that PAD inhibitors may function as potent anti-tumor drugs by blocking both cancer stem cell progression and tumor growth. Given the striking etiological and pathological similarities between human and canine cancer, we predict that PAD inhibitors may also prevent or slow the progression of canine mammary cancer. In order to begin testing this hypothesis, we now propose to study citrullination and PAD function in more detail in canine CSC and tumor lines in order to better understand the origins of mammary cancer and to lay the foundations for novel, and more efficacious, treatments to combat canine mammary cancer.