Scientists have identified a distinct subpopulation of cancer stem cells (CSCs) that is responsible for metastasis of a deadly human pancreatic cancer. The research provides insight into the role of CSCs in cancer initiation, progression, and metastasis and suggests new directions for development of more effective therapeutics.
Pancreatic adenocarcinoma ranks as the fourth leading cause of cancer death and is relatively incurable due to early metastatic spread and high resistance to radiation and chemotherapy. In order to better understand the pathology of this deadly cancer, scientists have recently begun to explore the role of CSCs in pancreatic tumors. CSCs are thought to be a small population of tumor cells that have similar properties to normal stem cells in that they are self-replicating and capable of giving rise to populations of differentiated cells.
Dr. Christopher Heeschen from the Department of Surgery at Ludwig-Maximilians-University in Munich, Germany led a study to examine the role of CSCs in pancreatic cancer.
The researchers discovered that human pancreatic cancer tissue contains tumorigenic and chemotherapy resistant stem cells defined by expression of CD133, a surface marker expressed by a variety of normal and malignant stem cells. They identified a distinct subset of cells expressing both CD133 and the chemokine receptor CXCR4, which plays a key role in blood cell migration, in the invasive front of the tumor. Implantation of isolated CD133+/CXCR4+ cells into mice resulted in metastatic tumor development, identifying them as CSCs.
Cancer metastasis was abolished by inhibiting CXCR4 or by transplanting CD133+/CXCR4- cells instead, underlining the importance of CXCR4 for the invasive cell behavior. Clinical studies revealed that tumor samples with a high number of CXCR4+ cells were more migratory and came from patients that suffered from more advanced metastatic disease. This important correlation may provide more accurate individual prognoses, allowing for improved selection of therapeutic agents.
These findings demonstrate for the first time that a specific CD133+/CXCR4+ cancer stem cell population present at the tumor-host interface is critically involved in pancreatic tumor metastasis. "The further molecular characterization of the pancreatic CSCs identified in the present study will be crucial for the development of new therapeutic strategies to eliminate these tumorigenic and metastatic cells. This may eventually provide a more effective treatment for our patients suffering from this deadly disease. In this respect, the demonstrated possibility of expanding pancreatic CSCs in vitro will dramatically help us in the evaluation of drug efficacy," offers Dr. Heeschen.
The researchers include Patrick C. Hermann, Stephan L. Huber, Tanja Herrler of Ludwig-Maximilians-University in Munich; Alexandra Aicher of J.W. Goethe University in Frankfurt; Joachim W. Ellwart of Helmholtz Center for Environment and Health in Munich; and Markus Guba, Christiane J. Bruns, and Christopher Heeschen of Ludwig-Maximilians-University in Munich.
This work was supported by the Deutsche Forschungsgemeinschaft.
Reference: Hermann et al.: "Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer." Publishing in Cell Stem Cell 1, 313--323, September 2007. DOI 10.1016/j.stem.2007.06.002
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