These factors include physicochemical characteristics (hypoxia, pH of the extracellular medium) and many signaling molecules (for example, TGF-b1, FGF, IL-6, HIF, Wnt ligands, etc.)secreted by not only tumor cells but also various stromal cells, including endothelial, immune cells, tumor-associated macrophages, fibroblasts, and normal stem cells. Here, TGFB1 is linked to neoplasm.