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Abstract
Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related
mortality. Stem cells have been implicated in pancreatic tumor growth, but the specific
role of these cancer stem cells in tumor biology, including metastasis, is still uncertain.
We found that human pancreatic cancer tissue contains cancer stem cells defined by
CD133 expression that are exclusively tumorigenic and highly resistant to standard
chemotherapy. In the invasive front of pancreatic tumors, a distinct subpopulation
of CD133(+) CXCR4(+) cancer stem cells was identified that determines the metastatic
phenotype of the individual tumor. Depletion of the cancer stem cell pool for these
migrating cancer stem cells virtually abrogated the metastatic phenotype of pancreatic
tumors without affecting their tumorigenic potential. In conclusion, we demonstrate
that a subpopulation of migrating CD133(+) CXCR4(+) cancer stem cells is essential
for tumor metastasis. Strategies aimed at modulating the SDF-1/CXCR4 axis may have
important clinical applications to inhibit metastasis of cancer stem cells.