Nearly 20 years have passed since Weinberg and Bell attempted to make the first tissue-engineered blood vessels. Following this early attempt, vascular tissue engineering has emerged as one of the most promising approaches to fabricate orderly and mechanically competent vascular substitutes. In elastic and muscular arteries, elastin is a critical structural and regulatory matrix protein and plays an important and dominant role by conferring elasticity to the vessel wall. Elastin also regulates vascular smooth muscle cells activity and phenotype. Despite the great promise that tissue-engineered blood vessels have to offer, little research in the last two decades has addressed the importance of elastin incorporation into these vessels. Although cardiovascular tissue engineering has been reviewed in the past, very little attention has been given to elastin. Thus, this review focuses on the recent advances made towards elastogenesis and the challenges we face in the quest for appropriate functional vascular substitutes.

Introduction Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells.

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Transmigration of cancer cells through the vascular endothelium (diapedesis) is a key event in tumor metastasis. To investigate mechanisms involved in diapedesis, we used laser scanning confocal microscopy to examine the distribution of cadherins of WM239 melanoma cells as they migrated through a monolayer of activated human umbilical vein endothelial cells (EC) cultured on matrigel. Cadherins, including VE‐cadherin, but not N‐cadherin, were enriched in contacts between EC, whereas N‐cadherin, but not VE‐cadherin, was found in contacts between melanoma cells. During the early stages of diapedesis, EC located below the attached melanoma cells decreased in height and VE‐cadherin disappeared from the EC contact located underneath the melanoma cell. Transendothelial migration began with small melanoma cell processes penetrating the VE‐cadherin‐negative regions between the EC. Subsequently, melanoma cells became intercalated between EC. Despite the absence of both VE‐cadherin and N‐cadherin, other members of the cadherin family were present in the heterotypic contacts between EC and melanoma cells. EC surrounding the intercalated melanoma cell subsequently extended processes and spread over the melanoma cell to re‐form the endothelial monolayer. Interestingly, the leading margins of these EC processes contained high levels of N‐cadherin, but not VE‐cadherin. VE‐cadherin‐rich cell–cell contacts, however, re‐formed between advancing endothelial processes when they met above the melanoma cell. As the melanoma cells came into contact with the underlying matrigel, they spread out and adopted a fibroblast‐like morphology. Addition of anti‐N‐cadherin antibodies to the assay resulted in a delay in the transendothelial migration of melanoma cells. Together, these results suggest that EC actively participate in diapedesis by disassembling and reassembling VE‐cadherin‐rich adherens junctions, and that N‐cadherin plays an important role in the transmigration of melanoma cells and the reclosure of the endothelium. Cell Motil. Cytoskeleton 38:351–364, 1997. © 1997 Wiley‐Liss, Inc.

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