title: Etoposide differentially affects bone marrow and dermal derived endothelial cells.
abstract: Chemotherapy alteration of the bone marrow microenvironment has the potential to influence hematopoietic recovery following transplantation. To discern the effect of specific drugs on components of the complex marrow microenvironment, in vitro models have significant utility. In the current study we sought to determine whether dermal (HMEC-1) and marrow derived endothelial cells (BMEC-1) respond differently to identical chemotherapy exposure. BMEC-1 cells were consistently more sensitive to etoposide exposure than HMEC-1 cells, measured as reduced viability. BMEC-1 also had reduced focal adhesion kinase (FAK) and VCAM-1 protein expression following chemotherapy, in contrast to dermal derived endothelial cells in which neither protein was influenced dramatically by etoposide. The two endothelial cell lines had markedly different levels of baseline VE-Cadherin protein, which was modestly altered by treatment. These data indicate that marrow derived endothelial cells have disruption of specific proteins following chemotherapy that may influence their ability to facilitate hematopoietic cell entry or egress from the marrow. In addition, these observations suggest that while BMEC-1 and HMEC-1 share a variety of characteristics, they differ significantly in their response to stress and should be incorporated into specific models with this consideration.
authors.affiliation: Department of Pediatrics, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26505, USA. swadams@hsc.wvu.edu
authors.forename: S W
authors.initials: SW
authors.lastname: Adams
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Fortney
authors.forename: Laura F
authors.initials: LF
authors.lastname: Gibson
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis; D020405:Dermis / Q000166:cytology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005047:Etoposide / Q000009:adverse effects*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008833:Microcirculation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D019040:E-Selectin; D005047:Etoposide; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019010:Vascular Cell Adhesion Molecule-1; D000099152:Cadherin 5