Pancreatic Cancer Stem Cells
The concept of cancer stem cells was first proposed 150 years ago and recent studies have demonstrated the existence of cancer stem cells that have the exclusive capacity for tumor initiation and propagation. Emerging data has been provided to support the
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J. P. Neoptolemos, R. Urrutia, J. L. Abbruzzese, M. W. Bu¨chler (eds.), Pancreatic Cancer, DOI 10.1007/978-0-387-77498-5_12, # Springer Science+Business Media, LLC 2010
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Pancreatic Cancer Stem Cells
Abstract: The concept of cancer stem cells was first proposed 150 years ago and recent studies have demonstrated the existence of cancer stem cells that have the exclusive capacity for tumor initiation and propagation. Emerging data has been provided to support the existence of cancer stem cells in human blood cell-derived cancers and solid organ tumors of the breast, prostate, brain, pancreas, head and neck, skin, and colon. Furthermore, pathways that regulate self-renewal, such as Bmi-1, Wnt, PTEN, Notch and Hedgehog which are known to regulate self-renewal of normal stem cells, have been implicated in the regulation of cancer stem cell self-renewal in a number of different tumor types. The study of human pancreatic cancers has revealed a unique subpopulation of cancer cells that possess the all characteristics of cancer stem cells. The pancreatic cancer stem cells express the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA), and represent 0.5–1.0% of the total pancreatic cancer cell population. Along with the characteristics of self-renewal and multilineage differentiation, pancreatic cancer stem cells display upregulation of Sonic hedgehog (SHH) and Bmi-1. Aberrant activation of these pathways in cancer stem cells are believed to be responsible for uncontrolled self-renewal of cancer stem cells which generate tumors that are resistant to radiation and chemotherapy. Conventional cancer therapeutics eliminate differentiated tumor cells, but do not target the cancer stem cells. The cancer stem cell concept points to a new direction of cancer therapeutics, which targets cancer stem cells. Pancreatic cancer stem cell research will aid our understanding of the molecular and cellular events leading to the development of pancreatic cancer and may change the therapeutic approach to the treatment of pancreatic cancer.
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Introduction
The concept that cancers arise from normal stem cells was first hypothesized more than 150 years ago [1], however, only recently have the techniques been developed to test the cancer stem-cell hypothesis in human solid tumors. Scientists first observed that when cancer cells of many different types were assayed for their proliferative potential, only a minority of cells showed extensive proliferation [2]. This observation suggested that malignant neoplasms are comprised of a small subset of distinct cancer stem cells (typically Fig. 12-1a, in which tumor cells are heterogeneous and most cancer cells can proliferate extensively to form new tumors. In the cancer stem cell theory (> Fig. 12-1b), tumor cells are also heterogeneous, but only a small portion of cancer cells are able to proliferate extensively and form new tumors. These cells are termed cancer stem cells because like normal stem cells, they can both self-renew and produce differentiated progeny. Studie
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