• 首都醫(yī)科大學(xué)宣武醫(yī)院普外科（北京 100053）;

目的總結(jié)有關(guān)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(nèi)、外近年來有關(guān)胰腺癌干細胞的文獻并進行綜述。結(jié)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(fā)現(xiàn)，胰腺癌中存在異質(zhì)性細胞，這些細胞具有干細胞的性質(zhì)，該細胞亞群在胰腺癌的發(fā)生、增殖、轉(zhuǎn)移和耐藥中發(fā)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(fā)現(xiàn)，胰腺癌干細胞內(nèi)的一些維持自我更新和轉(zhuǎn)移的信號通道表達異常。結(jié)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(xué)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(chǔ)與臨床雜志, 2011, 18(9): 931-935. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國普外基礎(chǔ)與臨床雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

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(wèi), 姜波健. 腫瘤干細胞與胃腸道癌發(fā)生和轉(zhuǎn)移 [J]． 中國普外基礎(chǔ)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(chǔ)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. 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. 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. 3. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells [J]. Nature, 2004, 432(7015): 396401.
  4. 4. Jemal A, Siegel R, Xu J, et al. Cancer statistics [J]. CA Cancer J Clin, 2010, 60(5): 277300.
  5. 5. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells [J]. Cancer Res, 2007, 67(3): 10301037.
  6. 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. 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. 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. 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. 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. 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. 12. 張鵬, 俞繼衛(wèi), 姜波健. 腫瘤干細胞與胃腸道癌發(fā)生和轉(zhuǎn)移 [J]． 中國普外基礎(chǔ)與臨床雜志， 2005, 16(1): 8186.
  13. 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. 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. 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. 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. 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. 18. Lee CJ, Dosch J, Simeone DM. Pancreatic cancer stem cells [J]. J Clin Oncol, 2008, 26(17): 28062812.
  19. 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. 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. 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. 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. 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. 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. 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(chǔ)與臨床雜志, 2010, 17(3): 302305.
  26. 26. Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers [J]. Science, 2004, 304(5678): 17551759.
  27. 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. 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. 29. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism [J]. Cell, 2006, 124(3): 471484.
  30. 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. 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. 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. 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. 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. 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. 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.