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Carcinogenesis Advance Access published online on April 5, 2006
Carcinogenesis, doi:10.1093/carcin/bgl031
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received January 30, 2006
Accepted March 20, 2006

REVIEW

Lymphatic vessels in cancer metastasis: bridging the gaps

Ramin Shayan 1, Marc G. Achen 1, and Steven A. Stacker 1 *

1 Angiogenesis Laboratory, Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia

* To whom correspondence should be addressed.
Steven A. Stacker, E-mail: steven.stacker{at}ludwig.edu.au


  Abstract

Distant organ metastasis is the most important factor in determining patient survival in cancer. This is thought to occur via the body's own systems for transporting fluid and cells, the blood vascular and lymphatic systems. Cancer cells may exploit these vascular systems by expressing growth factors, which alter the normal pattern of angiogenesis and lymphatic vessel growth (lymphangiogenesis), thus creating conduits for tumor metastasis. With respect to lymphatic metastasis, techniques which allow the mapping of a tumor's lymphatic drainage and sampling of the ‘sentinel node’ from the regional lymph node group, provide crucial prognostic information, determine further treatment, and offer a window into tumor-host immune interactions. Aberrant drainage patterns so identified, are both clinically significant, and highlight important anatomical and molecular complexities not explained by existing models of lymphatic development or anatomy. The molecular controls of tumor lymphangiogenesis and factors determining which lymphatic vessel subtypes are induced, may be targets for novel therapeutics designed to restrict cancer metastasis. Furthermore, analyses of these control mechanisms will enhance our understanding of the interactions between tumor cells and the lymphatic vasculature.

Keywords: lymphangiogenesis; vascular endothelial growth factors; receptors; metastasis; lymphatic endothelium; cancer; lymphedema.
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