Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer
Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer
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DOI：
10.1016/j.stem.2007.06.002
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发表时间：
2007-09-01
期刊：
影响因子：
23.9
通讯作者：
Heeschen, Christopher
中科院分区：
文献类型：
--
作者：
Hermann, Patrick C.;Huber, Stephan L.;Heeschen, Christopher
胰腺癌目前是癌症相关死亡的第四大原因。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CD 133表达定义的癌症干细胞，这些干细胞仅具有致瘤性并且对标准化疗具有高度耐药性。在胰腺肿瘤的侵袭性前沿，确定了CD 133（+）CXCR 4（+）癌症干细胞的独特亚群，其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癌症干细胞库实际上废除了胰腺肿瘤的转移表型，而不影响其致瘤潜力。总之，我们证明了迁移的CD 133（+）CXCR 4（+）癌症干细胞亚群是肿瘤转移所必需的。旨在调节SDF-1/CXCR 4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。
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.