@article{6756124a024f4b92b62bb6aff9afaa69,
title = "Expression of Hematopoietic Stem and Endothelial Cell Markers in Canine Hemangiosarcoma",
abstract = "Several chemicals and pharmaceuticals increase the incidence of hemangiosarcomas (HSAs) in mice, but the relevance to humans is uncertain. Recently, canine HSAs were identified as a powerful tool for investigating the pathogenesis of human HSAs. To characterize the cellular phenotype of canine HSAs, we evaluated immunoreactivity and/or messenger RNA (mRNA) expression of markers for hematopoietic stem cells (HSCs), endothelial cells (ECs), a tumor suppressor protein, and a myeloid marker in canine HSAs. Neoplastic canine cells expressed EC markers and a myeloid marker, but expressed HSC markers less consistently. The canine tumor expression results were then compared to previously published immunoreactivity results for these markers in human and mouse HSAs. There are 2 noteworthy differences across species: (1) most human HSAs had HSC marker expression, indicating that they were comprised of tumor cells that were less differentiated than those in canine and mouse tumors; and (2) human and canine HSAs expressed a late-stage EC maturation marker, whereas mouse HSAs were negative, suggesting that human and canine tumors may retain greater differentiation potential than mouse tumors. These results indicate that HSA development is variable across species and that caution is necessary when discussing translation of carcinogenic risk from animal models to humans.",
keywords = "canine, endothelial progenitor cells, hemangiosarcoma, hematopoietic stem cells, immunohistochemistry, tumor",
author = "Satoko Kakiuchi-Kiyota and Obert, {Leslie A.} and Crowell, {Danielle M.} and Shuhua Xia and Roy, {Marc D.} and Coskran, {Timothy M.} and Kreeger, {John M.} and Crabbs, {Torrie A.} and Cohen, {Samuel M.} and Cattley, {Russell C.} and Cook, {Jon C.}",
note = "Funding Information: The authors gratefully acknowledge Alan Opsahl (Pfizer) for his assistance with the preparation of the microscopic figures for this manuscript. The authors also express their gratitude to Cynthia Hutchinson (Auburn University) and Renee Huynh (Pfizer) for retrieving the paraffin blocks and cutting sections of canine tumor and normal tissues. Although the immunoreactivity method for CD117 in mouse tissues could not be successfully optimized, the authors sincerely thank the IHC Lab of the Pathology Support Group of the Cellular and Molecular Pathology Branch of the National Toxicology Program, NIEHS, for their extensive efforts and time attempting to optimize the immunoreactivity method. Authors{\textquoteright} Note Satoko Kakiuchi-Kiyota and Leslie A. Obert contributed equally to this work. Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.K.-K., L.A.O., and M.D.R. are employees of Genentech/Roche, GlaxoSmithKline, and Sarepta Therapeutics, respectively. They were previously employed by Pfizer. S.X., T.M.C., J.M.K., D.M.C., and J.C.C. are employees of Pfizer. T.A.C. is an employee of EPL. S.M.C. is an employee of University of Nebraska Medical Center, and is a consultant for Pfizer but on issues not related to the present study. He did not receive payment for activities related to the present project. R.C.C. is an employee of Auburn University, and has not served as a consultant for activities related to the present project. Pregabalin for the treatment of neuropathic pain was developed by Pfizer, and it was reported that an increased incidence of a single tumor type, HSAs, was seen in male and female mice, but not in rat, in 2-year carcinogenicity studies. EPL has been involved with numerous toxicity studies that have involved the evaluation of vascular tumors in various species, including mice and canines. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by funding from Pfizer Worldwide Research & Development. ORCID iD Satoko Kakiuchi-Kiyota https://orcid.org/0000-0002-4028-8817 Leslie A. Obert https://orcid.org/0000-0001-9788-2908 Samuel M. Cohen https://orcid.org/0000-0002-5047-0962 Funding Information: The authors gratefully acknowledge Alan Opsahl (Pfizer) for his assistance with the preparation of the microscopic figures for this manuscript. The authors also express their gratitude to Cynthia Hutchinson (Auburn University) and Renee Huynh (Pfizer) for retrieving the paraffin blocks and cutting sections of canine tumor and normal tissues. Although the immunoreactivity method for CD117 in mouse tissues could not be successfully optimized, the authors sincerely thank the IHC Lab of the Pathology Support Group of the Cellular and Molecular Pathology Branch of the National Toxicology Program, NIEHS, for their extensive efforts and time attempting to optimize the immunoreactivity method. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by funding from Pfizer Worldwide Research & Development. Publisher Copyright: {\textcopyright} The Author(s) 2020.",
year = "2020",
month = apr,
day = "1",
doi = "10.1177/0192623319897539",
language = "English (US)",
volume = "48",
pages = "481--493",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications Inc.",
number = "3",
}