Recent Progress on Pancreatic Cancer Stem Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Xiaohui , LI Fei.

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;

Corresponding author：

Keywords：

Pancreatic cancer; Stem cell; Marker; Metastasis; Chemoresistance

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ObjectiveTo review the recent advances in the pancreatic cancer stem cells field and identify the research trend in future. MethodsCurrent literatures on pancreatic cancer stem cells were collected and reviewed. ResultsPancreatic cancer was a highly lethal disease and was usually diagnosed at a late stage, for which there were few effective therapies. Emerging evidence had suggested that pancreatic cancer cells proposed a heterogeneous organization. A subpopulation of stem celllike cells sustains tumor growth, propagation, metastasis, and resistance to standard chemotherapy. Cancer stem cells were identified based on their expression of different sets of cell surface markers and functional characteristics. Some important signaling pathways which maintain self-renewal and metastasis were upregulated in pancreatic cancer stem cells. ConclusionsCurrent findings clearly suggest that specific elimination of cancer stem cells is possible and therapeutically relevant. An improved understanding of the biological behavior of such cells may lead to the development of novel diagnosis and treatment regimens for pancreatic cancer.

Citation： WANG Xiaohui,LI Fei.. Recent Progress on Pancreatic Cancer Stem Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(9): 931-935. doi: Copy

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.	张鹏, 俞继卫, 姜波健. 肿瘤干细胞与胃肠道癌发生和转移 [J]．中国普外基础与临床杂志， 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.	韩明利, 吴诚义. 乳腺癌干细胞与基因分型 [J]. 中国普外基础与临床杂志, 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. 张鹏, 俞继卫, 姜波健. 肿瘤干细胞与胃肠道癌发生和转移 [J]．中国普外基础与临床杂志， 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. 韩明利, 吴诚义. 乳腺癌干细胞与基因分型 [J]. 中国普外基础与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Recent Progress on Pancreatic Cancer Stem Cells

Abstract Full text Figures/Tables Video References Cited by

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