Abstract
Recent advances in tumor biology led to the realization that, in order to understand the mechanisms involved in proliferation and invasion of tumor cells, an analysis of the complex interactions that tumor cells establish with host cells of tumor microenvironment is required. The bidirectional interactions between tumor cells and components of tumor microenvironment, in particular endothelial cells, cells of monocyte/macrophage lineage and fibroblasts/myofibroblasts, play a critical role in most of the events that characterize tumor progression and metastasis. Interactions between these "reactive" normal cells and the genetically altered tumor cells, by either cell-to-cell contacts or soluble mediators, control the most aspects of tumor formation and progression. This review addresses some of the experimental evidences documenting that tumor cells may influence host cells of their own microenvironment by triggering changes that facilitate their local as well as distant dissemination. Therefore, it focuses on macrophages and fibroblasts that, upon stimulation by tumor cells, change their state towards a tumor-promoting-like phenotype.
Highlights
Recent advances in tumor biology led to the realization that, in order to understand the mechanisms involved in proliferation and invasion of tumor cells, an analysis of the complex interactions that tumor cells establish with host cells of tumor microenvironment is required
Mutual interactions between carcinoma cells and cancerassociated fibroblasts” (CAF) were reported by Nakamura et al.: tumoral IL-1, basic fibroblast growth factor and platelet-derived growth factor (PDGF) stimulate hepatocyte growth factor (HGF) expression in CAF, and in turn, stromal HGF leads to an invasive phenotype in carcinoma cells [94]
Tumor stroma is a specialized form of tissue composed of host cells and signals of different origin, which is associated with tumor cell growth, primarily of epithelial origin
Summary
Recent advances in tumor biology led to the realization that, in order to understand the mechanisms involved in proliferation and invasion of tumor cells, an analysis of the complex interactions that tumor cells establish with host cells of tumor microenvironment is required. That the contrasting effects exerted by TAM on the growth and metastatic diffusion of tumor cells may reflect different states of activation acquired by macrophages in the tumoral microenvironment. Vascular endothelial growth factor (VEGF), a key player in the angiogenesis process, is expressed by both tumor cells and TAM in several histological types of human tumors [53].
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