LYMPHANGIOGENESIS REVIEWS THE EMERGENCE OF MOLECULAR AND TRANSGENIC LYMPHOLOGY: WHAT DO WE (REALLY) KNOW SO FAR?

Abstract

Since its first sequential visualization in1902 by Florence Sabin, the development andmaintenance of the lymphatic system hasintrigued scientists and clinicians worldwide.Its close ties to the vascular network, relevancein the spread and control of parasiticand cancerous diseases, and involvement inthe development of other disease statesmanifested by lymphedema are well known.What is still not clear is how the systemdevelops in the first place, and this limits itseffective manipulation for the managementof disease states. The aim of the currentarticle is to summarize advances that havebeen made via genetic approaches usingtransgenic and knockout mice. It should benoted that studies of lymphatic vessel growthutilizing protein reagents or transgenictechnology alone, in a tissue/cell cultureenvironment, during tumor metastasis, in alymphatic disease paradigm, or during tissuerepair, have shown that various growthfactors, such as platelet-derived growth factorBB (1), hepatocyte growth factor (2),fibroblast growth factor (3), and VEGF-A (4)appear to play a role. This article is acommentary on the usefulness of specific genetic engineering tools in understandingthe development of the lymphatic system —with a focus on the questions that have beenaddressed using these tools, the extent towhich the questions have actually beenanswered, and the questions that havesubsequently been raised. It is not meant tobe a discussion of protein reagents or ofspecific biological situations that exhibitlymphangiogenesis (see reviews 5-7).