[Frontiers in Bioscience 16, 723-739, January 1, 2011]

Lymphangiogenesis and cancer metastasis

Mahir AA Al-Rawi1, Wen G Jiang2

1Department of Surgery, Betsi Cadwaladr University Health Board Glan Clwyd Hospital, Rhyl, Denbighshire, LL18 5UJ, UK, 2Department of Surgery, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK


1. Abstract
2. Introduction
3. Tumour lymphangiogenesis
4. Molecular mechanisms of lymphangiogenesis
5. The vascular endothelial factors and receptors and lymphangiogenesis
5.1.The vascular endothelial growth factors-C & -D (VEGF-C and VEGF-D)
6. Lymphatic markers
6.1. Podoplanin
6.2. Prox-1 (Prospero related homeobox gene -1)
6.3. Lymphatic Vessel Endothelial receptor -1 (LYVE-1)
6.4. Vascular endothelial growth factor receptpr-3 (VEGFR-3)
6.5. Other less specific markers
6.5.1. 5'-Nucleotidase
6.5.2. Weibel-Palade bodies and their contents
6.5.3.Basement membrane components
6.5.5. Gap junctions
6.5.6. PAL-E
6.5.7. Monoclonal antibodies
7. Lymphangiogenesis signalling
8. Lymphangiogenesis and malignancies
9. Lymphangiogenic signalling and tumour metastasis
10. Targeting lymphangiogenesis in cancer treatment
11. Perspectives and conclusions
12. References


Lymphangiogenesis remains a fascinating biological process that plays a crucial role in both normal tissue development and several lymphatic diseases. The last few years have witnessed a rapid progression in understanding the development and regulation of the lymphatic system which provided insight on several pathological processes including cancer lymphatic metastasis. Lymphatic vasculature serves as a major route for tumour metastasis. The dissemination of malignant cells to the regional lymph nodes is an early step in the progression of many solid tumours and is an important determinant of staging and prognosis. Lymphangiogenesis is thought to play a pivotal role for cancer cells to metastasise to the regional lymph nodes. Several human solid tumours are now considered to be lymphangiogenic i.e. they have the ability to induce their own lymphatic vessels to establish metastasis. Hence, targeting lymphangiogenesis by developing anti-lymphangiogenic agents might constitute a novel way to prevent lymphatic progression in some tumours. Here, we have reviewed the development of the lymphatic system, the regulation of lymphangiogenesis and explored its relation to several human cancers.