胰腺癌干細胞的研究進展_《中國普外基礎與臨床雜志》

作者：

王曉輝 , 李非

首都醫科大學宣武醫院普外科（北京 100053）;

關鍵詞：

胰腺癌干細胞標志物轉移化療耐藥

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的總結有關胰腺癌干細胞的研究進展并明確今后的研究方向。方法收集國內、外近年來有關胰腺癌干細胞的文獻并進行綜述。結果胰腺癌惡性程度高，早期診斷困難，缺乏有效治療手段。近年來的研究發現，胰腺癌中存在異質性細胞，這些細胞具有干細胞的性質，該細胞亞群在胰腺癌的發生、增殖、轉移和耐藥中發揮重要作用，通常利用細胞表面的特異標志物來鑒別胰腺癌干細胞。另外，研究還發現，胰腺癌干細胞內的一些維持自我更新和轉移的信號通道表達異常。結論針對干細胞的治療是可行的，深入了解胰腺癌干細胞的生物學行為將為胰腺癌的診斷和治療提供新的策略和手段。

引用本文： 王曉輝,李非. 胰腺癌干細胞的研究進展. 中國普外基礎與臨床雜志, 2011, 18(9): 931-935. doi: 復制

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15.	Wellner U, Schubert J, Burk UC, et al. The EMTactivator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs [J]. Nat Cell Biol, 2009, 11(12): 14871495.
16.	Trumpp A, Wiestler OD. Mechanisms of Disease: cancer stem cells-targeting the evil twin [J]. Nat Clin Pract Oncol, 2008, 5(6): 337347.
17.	Wang YH, Li F, Luo B, et al. A side population of cells from a human pancreatic carcinoma cell line harbors cancer stem cell characteristics [J]. Neoplasma, 2009, 56(5): 371378.
18.	Lee CJ, Dosch J, Simeone DM. Pancreatic cancer stem cells [J]. J Clin Oncol, 2008, 26(17): 28062812.
19.	Shah AN, Summy JM, Zhang J, et al. Development and characterization of gemcitabineresistant pancreatic tumor cells [J]. Ann Surg Oncol, 2007, 14(12): 36293637.
20.	Kallifatidis G, Labsch S, Rausch V, et al. Sulforaphane increases drugmediated cytotoxicity toward cancer stemlike cells of pancreas and prostate [J]. Mol Ther, 2011, 19(1): 188195.
21.	Rausch V, Liu L, Kallifatidis G, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics [J]. Cancer Res, 2010, 70(12): 50045013.
22.	Pece S, Tosoni D, Confalonieri S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content [J]. Cell, 2010, 140(1): 6273.
23.	Rohrberg KS, Skov BG, Lassen U, et al. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer [J]. Cancer Biomark, 2010, 7(3): 141151.
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25.	韓明利, 吳誠義. 乳腺癌干細胞與基因分型 [J]. 中國普外基礎與臨床雜志, 2010, 17(3): 302305.
26.	Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers [J]. Science, 2004, 304(5678): 17551759.
27.	Feldmann G, Dhara S, Fendrich V, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers [J]. Cancer Res, 2007, 67: 21872196.
28.	Mueller MT, Hermann PC, Witthauer J, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer [J]. Gastroenterology, 2009, 137(3): 11021113.
29.	Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism [J]. Cell, 2006, 124(3): 471484.
30.	Koide H, Asai T, Furuya K, et al. Inhibition of Akt (ser473) phosphorylation and rapamycinresistant cell growth by knockdown of mammalian target of rapamycin with small interfering rna in vascular endothelial growth factor receptor1targeting vector [J]. Biol Pharm Bull, 2011, 34(5): 602608.
31.	Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi1 regulate selfrenewal of normal and malignant human mammary stem cells [J]. Cancer Res, 2006, 66(12): 60636071.
32.	Cui HJ, Hu B, Li T, et al. BMI1 is Essential for the tumorigenicity of neuroblastoma cells [J]. Am J Pathol, 2007, 170(4): 13701378.
33.	Huber S, Bruns CJ, Schmid G, et al. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis [J]. Kidney Int, 2007, 71(8): 771777.
34.	Moriyama Y, Ohata Y, Mori S, et al. Rapamycin treatment causes developmental delay, pigmentation defects, and gastrointestinal malformation on Xenopus embryogenesis [J]. Biochem Biophys Res Commun, 2011, 404(4): 974978.
35.	Li J, Ko CJ, Saif MW. Recurrent cutaneous toxic erythema induced by gemcitabine in a patient with pancreatic cancer [J]. Cutan Ocul Toxicol, 2009, 28(3):144148.
36.	Mimeault M, Johansson SL, Henichart JP, et al. Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells [J]. Mol Cancer Ther, 2010, 9(3): 617630.

1. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J]. Nat Med, 1997, 3(7): 730737.
2. AlHajj M, Wicha MS, BenitoHernandez A, et al. Prospective identification of tumorigenic breast cancer cells [J]. Proc Natl Acad Sci USA, 2003, 100(7): 39833988.
3. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells [J]. Nature, 2004, 432(7015): 396401.
4. Jemal A, Siegel R, Xu J, et al. Cancer statistics [J]. CA Cancer J Clin, 2010, 60(5): 277300.
5. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells [J]. Cancer Res, 2007, 67(3): 10301037.
6. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer [J]. Cell Stem Cell, 2007, 1(3): 313323.
7. Jimeno A, Feldmann G, SuárezGauthier A, et al. A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development [J]. Mol Cancer Ther, 2009, 8(2): 310314.
8. Olempska M, Eisenach PA, Ammerpohl O, et al. Detection of tumor stem cell markers in pancreatic carcinoma cell lines [J]. Hepatobiliary Pancreat Dis Int, 2007, 6(1): 9297.
9. RicciVitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human coloncancerinitiating cells [J]. Nature, 2007, 445(7123): 111115.
10. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells [J]. Proc Natl Acad Sci USA, 2007, 104(24): 1015810163.
11. Gou S, Liu T, Wang C, et al. Establishment of clonal colonyforming assay for propagation of pancreatic cancer cells with stem cell properties [J]. Pancreas, 2007, 34(4): 429435.
12. 張鵬, 俞繼衛, 姜波健. 腫瘤干細胞與胃腸道癌發生和轉移 [J]．中國普外基礎與臨床雜志， 2005, 16(1): 8186.
13. Iwasa S, Yanagawa T, Fan J, et al. Expression of CXCR4 and its ligand SDF1 in intestinaltype gastric cancer is associated with lymph node and liver metastasis [J]. Anticancer Res, 2009, 29(11): 47514758.
14. Singh S, Srivastava SK, Bhardwaj A, et al. CXCL12CXCR4 signalling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy [J]. Br J Cancer, 2010, 103(11): 16711679.
15. Wellner U, Schubert J, Burk UC, et al. The EMTactivator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs [J]. Nat Cell Biol, 2009, 11(12): 14871495.
16. Trumpp A, Wiestler OD. Mechanisms of Disease: cancer stem cells-targeting the evil twin [J]. Nat Clin Pract Oncol, 2008, 5(6): 337347.
17. Wang YH, Li F, Luo B, et al. A side population of cells from a human pancreatic carcinoma cell line harbors cancer stem cell characteristics [J]. Neoplasma, 2009, 56(5): 371378.
18. Lee CJ, Dosch J, Simeone DM. Pancreatic cancer stem cells [J]. J Clin Oncol, 2008, 26(17): 28062812.
19. Shah AN, Summy JM, Zhang J, et al. Development and characterization of gemcitabineresistant pancreatic tumor cells [J]. Ann Surg Oncol, 2007, 14(12): 36293637.
20. Kallifatidis G, Labsch S, Rausch V, et al. Sulforaphane increases drugmediated cytotoxicity toward cancer stemlike cells of pancreas and prostate [J]. Mol Ther, 2011, 19(1): 188195.
21. Rausch V, Liu L, Kallifatidis G, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics [J]. Cancer Res, 2010, 70(12): 50045013.
22. Pece S, Tosoni D, Confalonieri S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content [J]. Cell, 2010, 140(1): 6273.
23. Rohrberg KS, Skov BG, Lassen U, et al. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer [J]. Cancer Biomark, 2010, 7(3): 141151.
24. Jiao Y, Shi C, Edil BH, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors [J]. Science, 2011, 331(6021): 11991203.
25. 韓明利, 吳誠義. 乳腺癌干細胞與基因分型 [J]. 中國普外基礎與臨床雜志, 2010, 17(3): 302305.
26. Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers [J]. Science, 2004, 304(5678): 17551759.
27. Feldmann G, Dhara S, Fendrich V, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers [J]. Cancer Res, 2007, 67: 21872196.
28. Mueller MT, Hermann PC, Witthauer J, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer [J]. Gastroenterology, 2009, 137(3): 11021113.
29. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism [J]. Cell, 2006, 124(3): 471484.
30. Koide H, Asai T, Furuya K, et al. Inhibition of Akt (ser473) phosphorylation and rapamycinresistant cell growth by knockdown of mammalian target of rapamycin with small interfering rna in vascular endothelial growth factor receptor1targeting vector [J]. Biol Pharm Bull, 2011, 34(5): 602608.
31. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi1 regulate selfrenewal of normal and malignant human mammary stem cells [J]. Cancer Res, 2006, 66(12): 60636071.
32. Cui HJ, Hu B, Li T, et al. BMI1 is Essential for the tumorigenicity of neuroblastoma cells [J]. Am J Pathol, 2007, 170(4): 13701378.
33. Huber S, Bruns CJ, Schmid G, et al. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis [J]. Kidney Int, 2007, 71(8): 771777.
34. Moriyama Y, Ohata Y, Mori S, et al. Rapamycin treatment causes developmental delay, pigmentation defects, and gastrointestinal malformation on Xenopus embryogenesis [J]. Biochem Biophys Res Commun, 2011, 404(4): 974978.
35. Li J, Ko CJ, Saif MW. Recurrent cutaneous toxic erythema induced by gemcitabine in a patient with pancreatic cancer [J]. Cutan Ocul Toxicol, 2009, 28(3):144148.
36. Mimeault M, Johansson SL, Henichart JP, et al. Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells [J]. Mol Cancer Ther, 2010, 9(3): 617630.

《中國普外基礎與臨床雜志》

胰腺癌干細胞的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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Content

《中國普外基礎與臨床雜志》

胰腺癌干細胞的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料