Changes in matrix composition during the growth and regression of human hemangiomas

Hemangiomas offer an uncommon opportunity to study rapid vessel growth and spontaneous regression of a vascular human tumor. In contrast, venous malformations are another type of vascular tumor that grows slowly without spontaneous involution. Extracellular matrix (ECM) molecules modulate the responsiveness of endothelial cells to mitogenic stimuli such as basic fibroblast growth factor (bFGF), a well-recognized stimulant of angiogenesis. In this study we hypothesized that in hemangiomas, sites of angiogenesis may have a different ECM composition than sites of vascular regression.

Using immunohistochemistry, we analyzed proliferating hemangiomas, regressing hemangiomas, venous malformations, and normal skin for the basement membrane ECM molecules collagen IV and laminin and plasma-borne ECM molecules fibronectin and vitronectin. We used metabolic labeling to determine whether primary human dermal microvascular endothelial cells regulated FGFR-1 or FGFR-2 when grown on these different matrices.

We found that proliferating hemangiomas showed extensive deposition of vitronectin in the subendothelial space. In contrast, regressing hemangiomas or venous malformations did not show vitronectin deposition. Venous malformations, which are composed of ectatic lakes of venous channels, also lacked laminin in their basement membranes. We also found that cultured microvascular endothelial cells grown on vitronectin increased synthesis of FGFR-1 and FGFR-2 protein.

Changes in the ECM environment occur in conjunction with the angiogenic state of a vascular human tumor. Furthermore, changes in the ECM environment alone can directly regulate synthesis of angiogenic growth factor receptors.