02489: Tumor-permissive Collagen Signatures in Canine Mammary Gland Tumors: Development of Prognostic Markers and Targeted Therapies for Improved Outcomes

Grant Status: Closed

Grant Amount: $162,700
Susan W. Volk, VMD, PhD; University of Pennsylvania
March 1, 2018 - August 31, 2020

Sponsor(s): American Boxer Charitable Foundation, American Brittany Club, Field Spaniel Society of America, Health & Rescue Foundation of the Petit Basset Griffon Vendeen Club of America, Irish Setter Club of America Foundation, Inc., Portuguese Water Dog Foundation, Inc., Weimaraner Foundation Fund Corporation

Breed(s): -All Dogs
Research Program Area: Oncology
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One Health: Yes

Abstract

Mammary gland tumors (MGT) are the most common malignancies in intact female dogs, and the resulting premature death and morbidity in this sub-population of dogs represents a significant health problem. While genetic alterations within tumor cells can promote their uncontrolled growth and ability to spread to distant sites, recent work indicates that normal, non-malignant cells and extracellular matrix (ECM) within the surrounding tumor stroma also regulate the growth and spread of cancer. The investigators have identified cancer-associated stromal (collagen) signatures in canine MGT biopsy samples that predict clinical outcome better than commonly used markers. These predictive markers may improve the veterinary oncologist?s ability to accurately predict which dogs truly need aggressive treatment from those that do not. Notably, their laboratories have shown that inhibition of a collagen-degrading enzyme (Fibroblast Activation Protein (FAP)) and increasing a tumor-suppressive collagen (type III collagen (Col3)) prevent the formation of these tumor-inciting signatures in other species (mouse and human). This work suggests that if these novel targets can suppress tumor-permissive collagen signatures in the dog, we can treat canine MGT more effectively. The goals of this project are 1) to identify additional collagen signatures which predict clinical outcome in dogs, 2) determine how they direct tumor cell behavior and 3) develop therapies that prevent formation of tumor-inciting collagen signatures in canine MGT. Based on the investigators' published and preliminary data, they predict that identifying and targeting tumor-inciting collagen signatures will lead to improvements in both diagnosis and treatment of dogs with malignant MGT.

Publication(s)

Terajima, M., Taga, Y., Brisson, B. K., Durham, A. C., Sato, K., Uzawa, K., Saito, T., Hattori, S., Sørenmo, K. U., Yamauchi, M., & Volk, S. W. (2021). Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues. Scientific Reports, 11(1), 8659. https://doi.org/10.1038/s41598-021-87380-y

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