Evaluation of Expression Profiles of Hematopoietic Stem Cell, Endothelial Cell, and Myeloid Cell Antigens in Spontaneous and Chemically Induced Hemangiosarcomas and Hemangiomas in Mice

Author:

Kakiuchi-Kiyota Satoko12,Crabbs Torrie A.3,Arnold Lora L.1,Pennington Karen L.1,Cook Jon C.2,Malarkey David E.4,Cohen Samuel M.1

Affiliation:

1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

2. Drug Safety Research and Development, Pfizer, Inc.,Groton, Connecticut, USA

3. Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina, USA

4. Cellular and Molecular Pathology Branch, National Toxicology Program and National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Abstract

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.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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