CHANGES IN MATRIX COMPOSITION DURING THE GROWTH AND REGRESSION OF HUMAN HEMANGIOMAS

Background. Hemangiomas offer an uncommon opportunity to study rapid v essel 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 (EC M) molecules modulate the responsiveness of endothelial cells to mitog enic stimuli such as basic fibroblast growth factor (bFGF), a well-rec ognized stimulant of angiogenesis. In this study we hypothesized that in hemangiomas, sites of angiogenesis may have a different ECM composi tion than sites of vascular regression. Materials and methods. Using i mmunohistochemistry, we analyzed proliferating hemangiomas, regressing hemangiomas, venous malformations, and normal skin for the basement m embrane ECM molecules collagen IV and laminin and plasma-borne ECM mol ecules fibronectin and vitronectin. We used metabolic labeling to dete rmine whether primary human dermal microvascular endothelial cells reg ulated FGFR-1 or FGFR-2 when grown on these different matrices. Result s. We found that proliferating hemangiomas showed extensive deposition of vitronectin in the subendothelial space. In contrast, regressing h emangiomas 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 fou nd that cultured microvascular endothelial cells grown on vitronectin increased synthesis of FGFR-1 and FGFR-2 protein. Conclusions. Changes in the ECM environment occur in conjunction with the angiogenic state of a vascular human tumor. Furthermore, changes in the ECM environmen t alone can directly regulate synthesis of angiogenic growth factor re ceptors. (C) 1998 Academic Press.