The differences in tumor cell metabolism, which arise as the consequence of tumor specific mutations as well as responses to microenvironmental changes, can directly impact epigenetic modifications.28 In addition to intra-epithelial factors controlling gene expression in tumor cells, microenvironmental cues, such as Tgf, Pdgfb, Met, Egf and Fgf from tumor-associated macrophages, fibroblasts or other stroma can also lead to silencing of epithelial genes such as E-Cadherin. This evidence concerns the gene CDH1 and neoplasm.