Tumour angiogenesis: vascular growth and survival.
Angiogenesis starts at the edge of a malignant epithelial tumour concurrently with tumour cell invasion and stromatogenesis, i.e. the formation of specific connective tissue stroma amenable to easy penetration by endothelial and tumour cells. However, as the tumour continues its growth, the edge becomes the inner tumour area, and a new invading tumour front is formed by the multiplying malignant cells which outflank the initial edge. This process, which repeats itself again and again, forms the "relay race" model of tumour vascular growth and regression. At the heart of the tumour unfavourable environmental conditions prevail -- hypoxia, acidity, lack of nutrients, failure of waste removal, and apoptosis rather than proliferation. Blood vessels and tumour cells are greatly decreased, but do not vanish, as tumour cells are shifting to anaerobic glycolysis, and blood vessels are turning into anti-apoptotic pathways -- vascular survival ability (VSA). Thus, assessing vascular density (VD) by simply counting "hot spots" at the edge of a tumour, where conditions are most favourable, is futile; it may reflect tumour angiogenic activity (TAA), but is not representative of genuine tumour vasculature. By combining vessel counts at the invading tumour front with those of the inner tumour areas a complete picture of tumour VD can be achieved. The thus formed four patterns of vascularization, designated as "edvin" (edge vsinner tumour area), are: edvin 1: low TAA/low VSA; edvin 4: high TAA/high VSA; edvin 2: low TAA/high VSA; and edvin 3: high TAA/low VSA. It is expected that this scheme will prove useful in the field of chemoradiotherapy and anti-angiogenic treatment.
Giatromanolaki
Alexandra
A
Department of Pathology, Democritus Inoversity of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Sivridis
Efthimios
E
Koukourakis
Michael I
MI
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply; D015179:Colorectal Neoplasms / Q000098:blood supply; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000098:blood supply