Consequently, a change in cancer cell phenotypes (as a result of cellular plasticity) can have a marked influence on surrounding non-cancer cells (Fig

Consequently, a change in cancer cell phenotypes (as a result of cellular plasticity) can have a marked influence on surrounding non-cancer cells (Fig. changes during tumor progression and treatment. Tumor cells are exposed to diverse metabolic conditions, signaling molecules, NSC117079 stromal elements, and therapeutic agents, which collectively form a volatile microenvironment that can fuel changes in cellular phenotype. Such changes may involve genetic alterations, but they more commonly involve transcriptional or epigenetic fluctuations. The resulting pliability in cell state can facilitate multiple aspects of tumor progression, including tumor initiation and metastasis, immune evasion, and chemoresistance. Consequently, elucidating the mechanisms by which cancer cells exploit plasticity to cope with selective pressures may lead to novel therapeutic opportunities. In leukemia, for example, treatment regimens that target a tumors differentiation state are highly effective, providing a rationale for pursuing such differentiation therapies in solid tumors. Here, we review our current understanding of cellular plasticity in cancer initiation and progression and suggest ways in which mechanistic insights could have implications for therapy. CELLULAR PLASTICITY IN PRE-MALIGNANCY: METAPLASIA In several adult tissues, cells change their identity as part of a physiologic response to injury or inflammation [1, 2]. Such changes may occur at the level of individual cells, where the phenomenon is commonly referred to as trans-differentiation, or at the level of an entire tissue, where the transformation is referred to as metaplasia. Metaplasia is thought to serve a protective function in the face of chronic damage, either by replacing lost tissue or forming barriers better suited to withstand hostile conditions. But in multiple organs C particularly those comprising the NSC117079 GI tract and other endoderm-derived tissues C the phenomenon is associated with a predisposition to cancer (Table 1). Importantly, metaplasia and trans-differentiation are not synonymous; while metaplastic tissues may arise through the conversion of one terminally differentiated cell type into another (i.e. trans-differentiation), alternative mechanisms C e.g. selective proliferation, drop-out of certain cell types, or alterations in stem cell differentiation Rat monoclonal to CD8.The 4AM43 monoclonal reacts with the mouse CD8 molecule which expressed on most thymocytes and mature T lymphocytes Ts / c sub-group cells.CD8 is an antigen co-recepter on T cells that interacts with MHC class I on antigen-presenting cells or epithelial cells.CD8 promotes T cells activation through its association with the TRC complex and protei tyrosine kinase lck patterns C could also account for metaplastic tissue changes. While lineage tracing studies in mice have provided insight into the programs underlying some forms of metaplasia, little is known about the cellular and molecular mechanisms leading to metaplasia in humans. Table 1. Examples of metaplasia in cancer results in carcinomas with histological characteristics of CC [19C21], suggesting that biliary trans-differentiation precedes cancer initiation. Importantly, these results do not preclude a biliary NSC117079 origin for CC, as suggested by other studies [22, 23], but rather suggest that CC may arise from either hepatocytes or BECs. Collectively, these studies suggest that a given cell type (i.e. the hepatocyte) may give rise to tumors with NSC117079 vastly different histological characteristics as a result of lineage plasticity elicited by distinct oncogenic pressures. In the future, it will be important to distinguish human CCs that are hepatocyte-derived from those that are BEC-derived, as tumors with distinct NSC117079 cellular origins are likely to exhibit distinct biological features which could further translate into divergent therapeutic opportunities. Ductal metaplasia in the pancreas The exocrine pancreas is responsible for synthesizing digestive enzymes and delivering them to the intestine. It does so through two principal cellular components: acinar cells, which produce enzymes, and ductal cells, which line the pancreatic ducts and carry the enzyme-rich pancreatic juice to the intestine. Cancers of the exocrine pancreas generally fall into two corresponding histological categories C pancreatic acinar carcinoma and pancreatic ductal carcinoma (PDAC)..