TY - JOUR
T1 - Evaluation of Expression Profiles of Hematopoietic Stem Cell, Endothelial Cell, and Myeloid Cell Antigens in Spontaneous and Chemically Induced Hemangiosarcomas and Hemangiomas in Mice
AU - Kakiuchi-Kiyota, Satoko
AU - Crabbs, Torrie A.
AU - Arnold, Lora L.
AU - Pennington, Karen L.
AU - Cook, Jon C.
AU - Malarkey, David E.
AU - Cohen, Samuel M.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported in part by the Division of the National Toxicology Program of the NIH, National Institute of Environmental Health Sciences; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the U.S. government.
Funding Information:
The authors gratefully acknowledge Dr. Norimitsu Shirai at Pfizer, Inc., for his pathological expertise and the individuals at EPL, Inc.: the Histology Lab for retrieving the paraffin blocks and cutting sections, the Photo Lab for taking photos of immunostaining, and Beth Mahler for editing images. We also gratefully acknowledge the technical expertise of Heather Jensen, Otis Lyght, Geoffrey Hurlburt, Yvette Rebolloso, David Olson, Quashana Brown, and Natasha Clayton in the Immunohistochemistry Lab of the Pathology Support Group of the Cellular and Molecular Pathology Branch of the National Toxicology Program, NIEHS for development of the methodology and performance of the immunohistochemistry. Heather Jensen was particularly helpful technically and in assisting in preparation of the manuscript. This research was supported (in part) by the Division of the National Toxicology Program of the NIH, National Institute of Environmental Health Sciences. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH); however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the U.S. government.
PY - 2013/7
Y1 - 2013/7
N2 - It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow–derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII–related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII–related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII–related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII–related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation. In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.
AB - It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow–derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII–related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII–related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII–related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII–related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation. In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.
KW - endothelial progenitor cells
KW - hemangiomas
KW - hemangiosarcomas
KW - hematopoietic stem cells
KW - immunohistochemistry
KW - mouse
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U2 - 10.1177/0192623312464309
DO - 10.1177/0192623312464309
M3 - Article
C2 - 23125116
AN - SCOPUS:84879482840
VL - 41
SP - 709
EP - 721
JO - Toxicologic Pathology
JF - Toxicologic Pathology
SN - 0192-6233
IS - 5
ER -