R.E. Mansel et al. (eds.), Metastasis of Breast Cancer, 219-240. © 2007 Springer.

the embryonic endothelial cell sprouting. Sabin proposed the "centrifugal sprouting" theory; that is, the development of the peripheral lymphatic system from isolated primitive lymph sacs exclusively by sprouting of endothelial cells into the surrounding tissues and organs (1-3). Most recent data favours this theory, including expression studies of lymphatic specific markers (4-5). The second theory of lymphatic development, the "centripetal sprouting", was proposed by Huntington and McClure (6). Huntington and McClure proposed a vasculogenic mechanism for the development of the peripheral lymphatic system. In this theory lymphatic spaces would arise independently from the veins, fusing into a primitive lymphatic network, and subsequently spread centripetally and connect to the venous system. The centripetally sprouting lymphatics would either integrate or replace the embryonic lymph sacs.

The lymphatic system is an excellent pathway for malignant cells dissemination, because the initial lymphatics are much larger than the blood capillaries and have incomplete basement membrane. Additionally, flow velocity of lymph is much slower than blood flow and has similar consistency to that of the interstitial fluid enabling cell viability (7-9). Conversely bloodstream is a highly aggressive medium for neoplastic cells due to serum toxicity, high shear stresses and mechanical deformation (9, 10). Additionally, haematogeneous metastasis has low efficiency because a significant number of neoplastic cells are either quiescent or apoptotic (11, 12). Furthermore, cancer cells may pass to bloodstream via lympho-venous shunts, high endothelial venules inside lymph nodes, or may be drained through the thoracic duct (7-9).

One of the major limitations of research on lymphatic vessels was the lack of histological, ultrastructural, and immunohistochemical markers to accurately discriminate between the lymphatic and blood endothelial cells. Lymphatic capillaries are identified by the fact that they are lined by a single layer of endothelial cells, which are characterised by having poorly developed junctions with frequent large gaps between cells. These loose junctions readily permit the passage of large biological macromole-cules, pathogens, and migrating cells. Because pressure within lymphatic capillaries is only slightly higher than the interstitium, lumen potency is maintained by anchoring filaments that connect the abluminal surfaces of endothelial cells to the perivascular extracellular matrix (7, 13). Unlike blood capillaries, lymphatic capillaries lack a continuous basement membrane, and they are devoid of pericytes (14). However, it should be noted that the latter is not true for larger collecting lymphatic ducts, which are supported by a thin connective tissue coat and higher up the lymphatic drainage tree by an additional smooth muscle wall. Although the initial lymphatics have no valves, the larger collecting ducts do (14). However these anatomical differences do not provide a practical way in the differentiation between blood and lymphatic vessels, particularly in regard to studies involving lymphatics.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment