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Signalling lymphangiogenesis

Vascular endothelial growth factors signal the development of tumour-induced lymph vessel growth and enhance lymphatic metastasis in vivo.A poorly understood characteristic of cancerous tissue is its ability to develop lymphatic tissue by the process of lymphangiogenesis. This is an important consideration because this contributes to the cancer's ability to metastasise through the body. In the February Nature Medicine, three separate research groups provide direct evidence that two recently clon

By | February 1, 2001

Vascular endothelial growth factors signal the development of tumour-induced lymph vessel growth and enhance lymphatic metastasis in vivo.

A poorly understood characteristic of cancerous tissue is its ability to develop lymphatic tissue by the process of lymphangiogenesis. This is an important consideration because this contributes to the cancer's ability to metastasise through the body. In the February Nature Medicine, three separate research groups provide direct evidence that two recently cloned members of the vascular endothelial growth factor (VEGF) family, VEGF-C and VEGF-D, are important regulators of lymphangiogenesis in vivo and enhance lymphatic metastasis.

Steven Stacker and colleagues at the Ludwig Institute for Cancer Research, Australia demonstrate that a molecule that attaches to the VEGFR-3 receptor, called VEGF-D, induces both angiogenesis and lymphangiogenesis. It also leads to the spread of cancerous cells to lymph nodes, a process that can be blocked by treatment with an antibody to VEGF-D (Nat Med 2001, 7:186-191).

Michael Detmar and colleagues at Massachusetts General Hospital, Boston, found that another molecule, which also attaches to VEGFR-3, VEGF-C, causes the growth of lymph vessels within tumours. VEGF-C is shown to be overexpressed in human breast cancer cells (Nat Med 2001, 7:192-198).

Using a mouse model Kari Alitalo and colleagues from the University of Helsinki, Finland show that a soluble form of VEGFR-3 can block the actions of both VEGF-C and VEGF-D and can prevent lymphangiogenesis. In addition, VEGFR-3 causes the degradation of existing tumour lymph vessels (Nat Med 2001, 7:199-205).

These findings could form the basis of a novel treatment for both cancer metastasis and lymphoedema, a chronic swelling of the limbs due to dysfunction to the lymphatic vessels.

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