查看更多>>摘要：Heterogeneity within and between tumors is a well-known phenomenon that greatly complicates the diagnosis and treatment of cancer. A large body of research indicates that heterogeneity develops through time as tumor-initiating stem cells, also known as cancer stem cells (CSCs), evolve genetic or epigenetic alterations that allow them to differentiate into multiple tumor cell types. Similar to normal stem cells, CSCs can self-renew and possess long-term repopulation potential. However, unlike normal stem cells, CSCs are not subject to the usual controls that limit growth. Different models have been postulated to explain the heterogeneity of tumors, but it is widely agreed that interactions between tumor cells and their microenvironment create niches that promote CSC properties and enable their survival. Within the microenvironment, CSC self-renewal, replication, and differentiation are postulated to produce a hierarchy of cells constituting the tumor mass. Increased understanding of the factors that create and contribute to tumor heterogeneity may support the design of therapies that affect CSC function and their microenvironments.
查看更多>>摘要：Cancer stem cells (CSCs) are a class of pluripotent cells that have been observed in most types of solid and hematologic cancers. CSCs have been shown in numerous cancer models to be involved in tumor development, cell proliferation, and metastatic dissemination, while possessing a capacity for sustained self-renewal. CSCs, which typically represent a small proportion of total cells of a given tumor, also exhibit resistance to chemotherapy and radiotherapy. Indeed, exposure to these treatments may promote "stemness" in nonstem cancer cells, which may explain why successful therapeutic reduction of tumor bulk will often fail to produce clinical improvement. Acquisition of stemness involves epithelial-mesenchymal transition (EMT), in which epithelial cells are transformed into a mesenchymal phenotype characterized by increased capacities for migration, invasiveness, and resistance to apoptosis. EMT may also contribute to metastasis by driving dissemination of mesenchymal CSCs to distant locations, whereupon the CSCs revert to an epithelial phenotype to support metastatic tumor growth. Several different approaches to treatment aimed at overcoming the intrinsic resistance of CSCs to conventional therapies are currently being developed. These include agents targeting tumorigenic pathways, such as JAK2/STAT3 and PI3K/mTOR, and immunotherapies, including vaccines and natural killer cells employed to induce a T cell response.
查看更多>>摘要：Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-kB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer.
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Lippincott Williams & Wilkins