Tumors and their microenvironment

It is well acknowledged that tumors display extensive cellular and molecular heterogeneity. Despite of cell-intrinsic (genetic and epigenetic) changes, tumor cells evolve into high-grade malignancies, along with the tumor microenvironment representing a landscape of cellular and structural components. Malignant cells experience a dynamic and complex scenario of communications with nonmalignant stromal cells, recruited and/or corrupted in loco by tumor-derived soluble factors, cytokines, metabolites, and matrix-remodeling agents. Together with acidity and hypoxia, microenvironmental signals favor tumor progression and exacerbate malignant phenotype, from the tumor initiation to the metastatic spreading