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lüll Pancreatic cancer stem cell and mesenchymal stem cell Hamada S; Shimosegawa TPancreatic Cancer and Tumor Microenvironment-/-ä 2012[]; ä (ä): äPancreatic cancer is one of the most life-threatening cancers and its prognosis has not been improved despite advances in diagnostic and therapeutic strategies. The reasons for resistance against conventional therapy and re-growth of untreatable tumor are now attributed to the existence of cancer stem cells (CSC), which occupy only a small part of the entire cancer tissue. CSC has characteristic features such as chemoresistance, establishment of metastasis and reconstruction of a hierarchical population of tumor cells. Specific surface markers have been identified, enabling the purification of CSC fractions from cell lines or clinical samples, serving to dissect the nature of CSCs. In addition, tumor stromal cells also contribute to the malignant behavior of cancer cells by promoting an invasive phenotype and the development of metastasis. Among those stromal cells, a mesenchymal stem cell (MSC) has unique contributions to the cancer tissue since this type of cell could accumulate in the tumor from distant organs such as bone marrow. MSC also acts as a defender of cancer cells by infiltrating into the tumor. This unique feature is now applied to generating cancer-specific delivery systems by utilizing MSC as a vehicle of therapeutic agents. The tumor microenvironment, which is created by the complex interaction between cancer cells and stromal cells, yields cancer promoting effects, especially induction of a hypoxic environment. Hypoxia- induced signals activate cellular adaptation machinery such as increased cell survival or enhanced stemness in pancreatic cancer cells. Tumor stromal cells also support engraftment of metastatic nodules which provide a partial CSC niche. Targeting the tumor stroma, CSCs, and MSCs will possibly lead to the development of novel therapeutic methods against pancreatic cancer.ä |