Advisor

Mackin, Andrew J.

Committee Member

Bulla, Camilo

Committee Member

Nanduri, Bindu

Committee Member

Lunsford, Kari V.

Committee Member

Hanson, Larry

Date of Degree

1-1-2017

Document Type

Dissertation - Open Access

Degree Name

Doctor of Philosophy

College

College of Veterinary Medicine

Abstract

Animal models have been recognized for the valuable roles they serve in both animal and human medicine. Dogs share many of the same naturally occurring tumors as humans including osteosarcoma, lymphoma, and mammary tumors. In addition, dogs share the same environment as humans, have a shorter lifespan, and often have a quicker progression of disease, making them an attractive model of human disease. Platelets are small anucleate cell fragments that have essential roles in hemostasis, angiogenesis, and wound healing, and, more recently recognized, roles in development, survival, growth, and metastasis of various cancers. Their roles in angiogenesis has proven to be both directly and indirectly linked to tumor growth due to the angiogenic roles they play in the development of tumor blood supply. Being able to study the interactions and mechanisms between platelets and tumor cells at the protein level, through proteomics, would allow great insight into the effects of platelets on tumor cell behavior as well as potential biomarker identification and therapeutic development. The objective of this research is to integrate the roles of canine platelet proteins into a better understanding of the effects and interactions that platelets have with different tumor cells while utilizing the canine model of neoplasms commonly affecting their human counterparts. The first study in this research describes an efficient technique developed for the purification of canine platelets from clinically relevant volumes of whole blood with high platelet recovery and minimal contamination from other blood cells. The second study describes a non-electrophoretic detergent fractionation technique used for the digestion of canine platelet samples for proteomic analysis as well as description of the proteomic findings for the normal canine platelet. Lastly, the third study describes the proteomic analysis of proteins differentially expressed by canine osteosarcoma and mammary tumor cells following incubation with canine platelet lysate in vitro. Overall, findings of this research support the canine model of human cancers and provide comprehensive information regarding canine platelet proteomics as well as novel efficient techniques that aid the future of canine platelet-tumor cell interaction research

URI

https://hdl.handle.net/11668/20716

Comments

detergent fractionation||platelet purification||biomarker||platelet activation||flow cytometry||DDF||platelet proteome||proteomics||proteome||purification||animal model||canine||platelet||mammary tumor||cancer||osteosarcoma||tumor

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