Hermann Patrick C, Huber Stephan L, Herrler Tanja, Aicher Alexandra, Ellwart Joachim W, Guba Markus, Bruns Christiane J, Heeschen Christopher
Department of Surgery, Ludwig-Maximilians-University, 81377 Munich, Germany.
Cell Stem Cell. 2007 Sep 13;1(3):313-23. doi: 10.1016/j.stem.2007.06.002.
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.
胰腺腺癌目前是癌症相关死亡的第四大主要原因。干细胞与胰腺肿瘤生长有关，但这些癌症干细胞在肿瘤生物学（包括转移）中的具体作用仍不确定。我们发现，人类胰腺癌组织含有由CD133表达定义的癌症干细胞，这些干细胞具有独特的致瘤性且对标准化疗具有高度抗性。在胰腺肿瘤的侵袭前沿，鉴定出了一个独特的CD133(+) CXCR4(+)癌症干细胞亚群，该亚群决定了个体肿瘤的转移表型。耗尽这些迁移的癌症干细胞的干细胞池实际上消除了胰腺肿瘤的转移表型，而不影响其致瘤潜力。总之，我们证明迁移的CD133(+) CXCR4(+)癌症干细胞亚群对肿瘤转移至关重要。旨在调节SDF-1/CXCR4轴的策略可能在抑制癌症干细胞转移方面具有重要的临床应用价值。
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