Phenotypic comparison between mesothelial and microvascular endothelial cell lineages using conventional endothelial cell markers, cytoskeletal protein markers and in vitro assays of angiogenic potential

Abstract

Abstract Endothelial and mesothelial cells are mesodermally derived simple squamous epithelial cells. A controversy concerning the ontogenetic origin of neoplasms derived from these cell types, commonly cited in the literature, is whether Kaposi's sarcoma is a mesothelioma or an angioma. To assess the similarities and differences between these cell types, pulmonary microvascular endothelial cells (PMVEC) and pericardial mesothelial cells (PMC) were cultured in vitro. PMVEC and PMC were found to be difficult to distinguish from one another by histological criteria alone. Both cell types formed contact-inhibited, and ‘cobblestone’, monolayers typical of simple epithelial cells. PMVEC and PMC demonstrated positive immunoreactivity to Factor VIII-related antigen and angiotensin-converting enzyme (ACE) antigen. They also showed uptake of 1,1′-dioctacecyl-1,3,3,3′,3-tetramethyl-indocarbocyanine perchlorate acetylated low density lipoprotein (DiI-AcLDL) in 4 h. Both PMVEC and PMC expressed low ACE activities when compared to macrovessel endothelial cells. PMVEC and PMC shared similar isoform profiles for vimentin and actin. Both cell types expressed the simple epithelial keratins, cytokeratins 8 and 19, though PMC contained 50% more cytokeratins than PMVEC. Additionally, PMC contained cytokeratin 18, an intermediate filament protein not detectable in PMVEC. PMC formed 15 times as many epithelial ringlets or “stomata” as PMVEC. PMVEC but not PMC could be induced in vitro to differentiate into branching tube-like structures in reponse to their culture environment. Reorganization of PMVEC into vessel-like structures was more rapid and complete thatn PMC when embedded in three-dimensional collagen I lattices, cultured on Matrigel or exposed to a shaped-pulsed electromagnetic field. The angiogenic response of PMVEC to specialized culture conditions in vitro may reflect their phenotypic differentiation state characterized by anastomosing vascular structures in vivo, whereas PMC remain differentiated into monolayer sheet-like structures.