Stroma: An active but neglected contributor to tumorigenesis, 'when dialogue takes over from monologue': Interactions between tumour cells and their tissue micro-environment Stroma : Partenaire actif mais sous-estimé de la tumorigenèse, ? quand le dialogue remplace le monologue ?: Interactions entre les cellules tumorales et leur microenvironnement tissulaire

摘要

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 there may be transdifferentiation of epithelial tumour cells or epithelial mesenchymal transition (EMT). This makes these motile invasive cells resistant to apoptosis and able to secrete chemoattractant and activating molecules, such as adrenomedullin. Fibroblast precursors, macrophages, inflammatory cells and cancerous EMT cells cooperate in the activation of a cascade 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. The process of interaction between a tumour and its microenvironment is a mirror image of what occurs during gastrulation in the embryo.