Background: The JAK-STAT pathway is a cellular signaling pathway, which acts normally in humans and animals in the control of multiple important functions. Dysregulation of this pathway has been identified in human cancers, as well as a limited number of veterinary cancers.
Objectives: The aims of this study were to identify the presence and tentative activity of components of the JAK-STAT pathway in selected canine tumors.
Methods: Formalin-fixed, paraffin-embedded samples from mast cell tumors (MCT), hemangiosarcomas (HSA), thyroid carcinomas, and apocrine gland anal sac adenocarcinomas (AGASACA) were obtained from the Diagnostic Histopathology Laboratory at the Virginia Maryland College of Veterinary Medicine. Immunohistochemistry was performed to evaluate protein levels of JAK1, phospho-JAK1, JAK2, phospho-JAK2, STAT3, and phospho-STAT3. Signalment, treatment information, and survival information was obtained from the medical record for each case.
Results: Tumor samples were scored for percent positive neoplastic cells. Positive staining was seen for all antibodies in all tumor types, with expression of JAK1, STAT3, and pSTAT3 being highest overall for all tumor types. Significant associations were seen between JAK1 and survival time in MCT (p = 0.03), pJAK1 and survival time in HSA (p = 0.009) and MCT (p = 0.04), and pSTAT3 and metastasis in MCT (p = 0.0008).
Conclusions: The finding of positive staining for the components of the JAK-STAT pathway in the tumor samples evaluated indicates presence and tentative activity of this pathway in the studied cancers. Further study of JAK1, pJAK1, and pSTAT3 should be pursued to evaluate their potential as therapeutic targets. / MS / The JAK-STAT pathway is a cellular signaling pathway which acts in humans and animals to control functions, such as development of the immune system, and development of the mammary glands during pregnancy. This pathway can become dysregulated, and contribute to development of cancer in both humans and animals. Development of cancer drugs that can target this pathway when dysregulated may aid in controlling further growth of spread of cancer, and may help to prolong survival in patients affected.
In our study, four different cancer types were investigated in dogs for the presence and activity of components of the JAK-STAT pathway. Evidence of presence and activity was identified in the cancers evaluated, suggesting that more work should be done to determine if the JAK-STAT pathway is activated in other canine tumor types, and whether the pathway can be targeted as a cancer treatment.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/100859 |
| Date | 22 May 2017 |
| Creators | Fagan, Erin A. |
| Contributors | Veterinary Medicine, Dervisis, Nikolaos G., LeRoith, Tanya, Klahn, Shawna L. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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