Molecular mechanisms in lymphangiogenesis: model systems and implications in human disease.
The basic science and development of therapies targeting the blood vascular system has enjoyed much focus due to the knowledge of the molecular mechanisms behind its development and roles in disease. However, the closely associated lymphatic system, while also being responsible for a number of serious and debilitating diseases, has not garnered as much attention due to the lack of specific molecular markers, thereby limiting this field to no more than descriptive analysis. Within the past decade, great strides have been taken to identify a number of molecular signatures unique to the lymphatic system. To this end, the timeline for lymphatic development has now been redefined at the molecular level, and diseases associated with lymphatics now have a molecular basis. With this knowledge, the current modes of treatment for disease such as lymphedema, lymphangiomas, and metastatic progression can now be augmented with potential molecular therapies that have currently been tested in a number of animal models. Much like the therapeutics that have been associated with vasculogenesis and angiogenesis, manipulation of the molecular pathways that define lymphatic development may lead to better clinical outcomes associated with developmental defects and disease.
Kim
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Department of Medical Biophysics, Division of Molecular and Cellular Biology, University of Toronto, Sunnybrook & Women's College Health Sciences Center, Toronto, ON, Canada.
Dumont
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D042702:Angiopoietin-2 / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D042583:Lymphangiogenesis; D008206:Lymphatic Diseases / Q000235:genetics*; D008208:Lymphatic System / Q000254:growth & development*; D008954:Models, Biological; D042764:Receptors, TIE / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000502:physiology; D000098551:Prospero-Related Homeobox 1 Protein
D042702:Angiopoietin-2; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D018398:Homeodomain Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C082078:mesenchyme fork head 1 protein; D000098551:Prospero-Related Homeobox 1 Protein; D042764:Receptors, TIE; D040321:Vascular Endothelial Growth Factor Receptor-3