Title

The Relationship between Canine Platelets and Cancer Cells

Advisor

Pruett, Stephen B.

Committee Member

Hanson, Larry

Committee Member

Lunsford, Kari V.

Committee Member

Mackin, Andrew J.

Date of Degree

1-1-2017

Original embargo terms

Visible to MSU only for 3 years

Document Type

Dissertation - Open Access

Degree Name

Doctor of Philosophy

College

College of Veterinary Medicine

Abstract

Platelets are small and anucleate blood cells that are well known for their role in hemostasis. Other less recognized platelet functions include contributions to cancer vascularization, growth, and metastasis. Although the participation of platelets in cancer biology has been broadly studied in mouse models, there is no information in the literature regarding the crosstalk of platelets and cancer cells in dogs. The objective of this dissertation was to explore the interaction of canine platelets and tumor cells in vitro. The main hypothesis was that canine platelets were similar to human and murine platelets, and would interact with tumor cells, resulting in a change in the behavior of these cells. Using confocal immunofluorescence, we show that fibrinogen and von Willebrand factor have little colocalization within platelets, providing evidence that canine platelets have selective packaging and different alpha-granule subtypes, as shown in mice and humans. Then, we demonstrate canine platelet activation by osteosarcoma and mammary carcinoma cells, utilizing platelet aggregometry. Next, we show that intact platelets, platelet lysate, and thrombin-activated platelet releasate have an inhibitory effect on the migration of canine osteosarcoma and mammary carcinoma cell lines, contrary to what is described in humans and mice. We also demonstrate that releasate from canine platelets activated by collagen induces cancer cell migration, the opposite of the effect of releasates derived from thrombin or adenosine diphosphate activation. Lastly, we show that platelets can downregulate epithelial-to-mesenchymal-related transcription factors in canine cancer cells, suggesting that platelets may play an important role regulating this process in canine cancer progression. In conclusion, the results of this study have revealed important interactions between canine cancer cell lines and platelets in vitro. Our findings suggest that platelets most likely have a significant role in cancer growth in dogs and that cancer cells most likely affect platelet function in cancer patients.

URI

https://hdl.handle.net/11668/19246

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