Microvascular endothelial cell invasion into the
fibrin provisional matrix is an integral component of angiogenesis during
wound repair.
Cell surface receptors which interact with
extracellular matrix proteins participate in cell migration and invasion. Malignant cells use CD44-related
chondroitin sulfate proteoglycan (CSPG) as a matrix receptor to mediate migration and invasion. In this study, we examine whether cell surface CSPG can mediate similar events in nonmalignant
wound microvascular endothelial cells or whether use of CSPG for migration and invasion is a property largely restricted to malignant cells. After inhibiting CSPG synthesis with
p-nitrophenyl beta-d xylopyranoside (
beta-d xyloside),
wound microvascular endothelial cells were capable of attaching and spreading on the surface of a
fibrin gel; however, their ability to invade the
fibrin matrix was virtually eliminated. To begin to examine the mechanism by which endothelial cells use CSPG to invade
fibrin matrices, cell adhesion and migration on
fibrinogen was examined. Endothelial cell adhesion and migration on
fibrinogen were inhibited by both
beta-d xyloside and after cleavage of
chondroitin sulfate from the core
protein by
chondroitinase ABC. We have determined that
wound microvascular endothelial cells express the majority of their
proteoglycan as CSPG and that the CSPG core
protein is immunologically related to CD44. PCR studies show that these cells express both the "standard" (CD44H)
isoform and an
isoform containing the variably spliced exon V3. In addition, anti-CD44 antibody blocks endothelial cell migration on
fibrinogen. Affinity chromatography studies reveal that partially purified microvascular endothelial cell CSPG binds
fibrinogen. These findings suggest that CD44-related CSPG, a molecule implicated in the invasive behavior of
tumor cells, is capable of binding
fibrinogen/
fibrin, thereby mediating endothelial cell migration and invasion into the
fibrin provisional matrix during
wound repair.