Angiogenesis: return to the fundamental

作者：Martin P M^*; Ouafik L' H

来源：Oncologie, 2012, 14(4): 199-215.

DOI：10.1007/s10269-012-2152-y

• Neoangiogenesis
• Inter actions between malignant cells/micro-environment (endothelial cells, fibroblast, macrophages)
• Tumoral hypoxia
• Proteases

In the evolution of a cancer, tumorigenesis is the stage at which the initial molecular and cellular process develops a tissue dimension and, in particular, takes on a clinical aspect. This stage is made possible by the establishment and development of interactions between transformed epithelial cells and their stromal tissue matrix. The cells which are recruited from the stroma and activated are fibroblast precursors, macrophages, haematopoietic stem cells and inflammatory cells. Through these cells the stroma becomes an active partner in tumour development. As a result of these interactions neoangiogenesis is a key factor for tumour progression, invasion and metastasis. The tumoral cell proliferation is limited by normoxy, fast growing induce hypoxic cell status, and the hypoxic tumoral cell secrete chimioattractant and activating molecules, such as adrenomedullin. Fibroblast precursors, macrophages, inflammatory cells and hypoxic cancerous cells cooperate in the activation of a cascad, of proteases and growth factors, which interact with endothelial cells and pericytes. This destabilises capillary vessels and initiates angiogenesis. The new vessels are constantly refashioned and partially compensate for the tumoral hypoxia caused by rapid tumour growth. However, they constitute an important route for the metastatic spread of tumour. All of these interactions are only a distortion of the physiological processes seen during tissue repair. This latter is limited in its time frame and definitively terminated by healing, whereas the interactions between malignant cells and the micro-environment do not have a mechanism to block them.

• 出版日期2012-4