肿瘤干细胞分离方法研究进展_West China Medical Journal

Authors：

 李丹青 ^1,2 ,  何跃东 ¹

1. ;
2. ;

Corresponding author：

何跃东, Email: he-yd@163.com

Keywords：

肿瘤干细胞; 干细胞标志物; 流式细胞分选; 免疫磁珠分选

DOI：

10.7507/1002-0179.20150393

Video：

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肿瘤干细胞是肿瘤治疗新理论，近年来受到广泛关注，也备受争议。该理论认为肿瘤干细胞是肿瘤细胞的来源，是肿瘤发生耐药、复发、转移的根本原因。目前通过悬浮细胞培养法、流式细胞分选法、免疫磁珠分选法等多种方法，已从多种实体瘤细胞系或组织中分离和鉴定出肿瘤干细胞，包括乳腺癌、脑肿瘤、结肠癌、胰腺癌、卵巢癌等，研究其生物学特性、特异性标志物及调控机制，有望为肿瘤治疗提供新的思路和策略。研究肿瘤干细胞，首先要对其分离和培养，现就目前肿瘤干细胞的分离方法研究进展予以综述。

Citation： 李丹青, 何跃东. 肿瘤干细胞分离方法研究进展. West China Medical Journal, 2015, 30(7): 1361-1364. doi: 10.7507/1002-0179.20150393 Copy

1.	Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2.	Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells——perspectives on current status and future directions:AACR Workshop on cancer stem cells[J]. Cancer Res, 2006, 66(19):9339-9344.
3.	Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice[J]. Nature, 1994, 367(6464):645-648.
4.	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.
5.	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.
6.	Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133⁺ cancer stem cells in glioblastoma[J]. Mol Cancer, 2006, 5:67.
7.	Vaiopoulos AG, Kostakis ID, Koutsilieris M, et al. Colorectal cancer stem cells[J]. Stem Cells, 2012, 30(3):363-371.
8.	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.
9.	Casagrande F, Cocco E, Bellone S, et al. Eradication of chemotherapy-resistant CD44⁺ human ovarian cancer stem cells in mice by intraperitoneal administration of Clostridium perfringens enterotoxin[J]. Cancer, 2011, 117(24):5519-5528.
10.	Garcia-Gomez I, Elvira G, Zapata AG, et al. Mesenchymal stem cells:biological properties and clinical applications[J]. Expert Opin Biol Ther, 2010, 10(10):1453-1468.
11.	Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system[J]. Science, 1992, 255(552):1707-1710.
12.	Lansdorp PM, Dragowska W. Long-term erythropoiesis from constant numbers of CD34⁺ cells in serum-free cultures initiated with highly purified progenitor cells from human bone marrow[J]. J Exp Med, 1992, 175(6):1501-1509.
13.	Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells[J]. Proc Natl Acad Sci USA, 2004, 101(39):14228-14233.
14.	Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]. Hepatology, 2006, 44(1):240-251.
15.	Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness[J]. Proc Natl Acad Sci USA, 2006, 103(30):11154-11159.
16.	Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system[J]. Stem Cells, 2006, 24(3):506-513.
17.	Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma[J]. Proc Natl Acad Sci USA, 2007, 104(3):973-978.
18.	Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J]. Cell Stem Cell, 2007, 1(5):555-567.
19.	Beier D, Hau P, Proescholdt M, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles[J]. Cancer Res, 2007, 67(9):4010-4015.
20.	Liu SY, Zheng PS. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer[J]. Oncotarget, 2013, 4(12):2462-2475.
21.	Pang R, Law WL, Chu AC, et al. A subpopulation of CD26⁺ cancer stem cells with metastatic capacity in human colorectal cancer[J]. Cell Stem Cell, 2010, 6(6):603-615.
22.	Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells[J]. Cancer Res, 2007, 67(3):1030-1037.
23.	Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells[J]. Cancer Res, 2005, 65(23):10946-10951.
24.	Richardson GD, Robson CN, Lang SH, et al. CD133, a novel marker for human prostatic epithelial stem cells[J]. J Cell Sci, 2004, 117 (Pt 16):3539-3545.
25.	Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance[J]. Nat Rev Cancer, 2005, 5(4):275-284.
26.	Singh A, Settleman J. EMT, cancer stem cells and drug resistance:an emerging axis of evil in the war on cancer[J]. Oncogene, 2010, 29(34):4741-4751.
27.	Hu X, Ghisolfi L, Keates AC, et al. Induction of cancer cell stemness by chemotherapy[J]. Cell Cycle, 2012, 11(14):2691-2698.
28.	谢玲玲, 卢淮武, 钟沅月, 等.分割剂量射线照射富集宫颈癌肿瘤干细胞的研究[J]. 中山大学学报:医学科学版, 2012, 33(3):330-335.
29.	路秀英, 李晓明. 低氧诱导因子对肿瘤干细胞作用的研究进展[J]. 医学综述, 2008(20):3081-3083.
30.	Bhaskara VK, Mohanam I, Rao JS, et al. Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells[J]. PLoS One, 2012, 7(2):e309D5.
31.	Radisky DC. Epithelial-mesenchymal transition[J]. J Cell Sci, 2005, 118(19):4325-4326.
32.	Santisteban M, Reiman JM, Asiedu MK, et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells[J]. Cancer Res, 2009, 69(7):2887-2895.
33.	Ye J, Wu D, Shen J, et al. Enrichment of colorectal cancer stem cells through epithelial-mesenchymal transition via CDH1 knockdown[J]. Mol Med Rep, 2012, 6(3):507-512.
34.	Li J, Zhou BP. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem celllike characters[J]. BMC Cancer, 2011, 11:49.
35.	Jin L, Hope KJ, Zhai Q, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells[J]. Nat Med, 2006, 12(10):1167-1174.
36.	Gadhoum Z, Delaunay J, Maquarre E, et al. The effect of antiCD44 monoclonal antibodies on differentiation and proliferation of human acute myeloid leukemia cells[J]. Leuk Lymphoma, 2004, 45(8):1501-1510.
37.	Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis[J]. Nature, 2004, 432(715):324-331.
38.	Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML[J]. N Engl J Med, 2004, 351(7):657-667.
39.	Mamaeva V, Rosenholm JM, Bate-Eya LT, et al. Mesoporous silica nanoparticles as drug delivery systems for targeted inhibition of Notch signaling in cancer[J]. Mol Ther, 2011, 19(8):1538-1546.
40.	Clement V, Sanchez P, De Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell selfrenewal, and tumorigenicity[J]. Curr Biol, 2007, 17(2):165-172.
41.	Zhou Y, Yang J, Kopeček J. Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells[J]. Biomaterials, 2012, 33(6):1863-1872.

1. Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2. Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells——perspectives on current status and future directions:AACR Workshop on cancer stem cells[J]. Cancer Res, 2006, 66(19):9339-9344.
3. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice[J]. Nature, 1994, 367(6464):645-648.
4. 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.
5. 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.
6. Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133⁺ cancer stem cells in glioblastoma[J]. Mol Cancer, 2006, 5:67.
7. Vaiopoulos AG, Kostakis ID, Koutsilieris M, et al. Colorectal cancer stem cells[J]. Stem Cells, 2012, 30(3):363-371.
8. 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.
9. Casagrande F, Cocco E, Bellone S, et al. Eradication of chemotherapy-resistant CD44⁺ human ovarian cancer stem cells in mice by intraperitoneal administration of Clostridium perfringens enterotoxin[J]. Cancer, 2011, 117(24):5519-5528.
10. Garcia-Gomez I, Elvira G, Zapata AG, et al. Mesenchymal stem cells:biological properties and clinical applications[J]. Expert Opin Biol Ther, 2010, 10(10):1453-1468.
11. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system[J]. Science, 1992, 255(552):1707-1710.
12. Lansdorp PM, Dragowska W. Long-term erythropoiesis from constant numbers of CD34⁺ cells in serum-free cultures initiated with highly purified progenitor cells from human bone marrow[J]. J Exp Med, 1992, 175(6):1501-1509.
13. Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells[J]. Proc Natl Acad Sci USA, 2004, 101(39):14228-14233.
14. Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]. Hepatology, 2006, 44(1):240-251.
15. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness[J]. Proc Natl Acad Sci USA, 2006, 103(30):11154-11159.
16. Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system[J]. Stem Cells, 2006, 24(3):506-513.
17. Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma[J]. Proc Natl Acad Sci USA, 2007, 104(3):973-978.
18. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J]. Cell Stem Cell, 2007, 1(5):555-567.
19. Beier D, Hau P, Proescholdt M, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles[J]. Cancer Res, 2007, 67(9):4010-4015.
20. Liu SY, Zheng PS. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer[J]. Oncotarget, 2013, 4(12):2462-2475.
21. Pang R, Law WL, Chu AC, et al. A subpopulation of CD26⁺ cancer stem cells with metastatic capacity in human colorectal cancer[J]. Cell Stem Cell, 2010, 6(6):603-615.
22. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells[J]. Cancer Res, 2007, 67(3):1030-1037.
23. Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells[J]. Cancer Res, 2005, 65(23):10946-10951.
24. Richardson GD, Robson CN, Lang SH, et al. CD133, a novel marker for human prostatic epithelial stem cells[J]. J Cell Sci, 2004, 117 (Pt 16):3539-3545.
25. Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance[J]. Nat Rev Cancer, 2005, 5(4):275-284.
26. Singh A, Settleman J. EMT, cancer stem cells and drug resistance:an emerging axis of evil in the war on cancer[J]. Oncogene, 2010, 29(34):4741-4751.
27. Hu X, Ghisolfi L, Keates AC, et al. Induction of cancer cell stemness by chemotherapy[J]. Cell Cycle, 2012, 11(14):2691-2698.
28. 谢玲玲, 卢淮武, 钟沅月, 等.分割剂量射线照射富集宫颈癌肿瘤干细胞的研究[J]. 中山大学学报:医学科学版, 2012, 33(3):330-335.
29. 路秀英, 李晓明. 低氧诱导因子对肿瘤干细胞作用的研究进展[J]. 医学综述, 2008(20):3081-3083.
30. Bhaskara VK, Mohanam I, Rao JS, et al. Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells[J]. PLoS One, 2012, 7(2):e309D5.
31. Radisky DC. Epithelial-mesenchymal transition[J]. J Cell Sci, 2005, 118(19):4325-4326.
32. Santisteban M, Reiman JM, Asiedu MK, et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells[J]. Cancer Res, 2009, 69(7):2887-2895.
33. Ye J, Wu D, Shen J, et al. Enrichment of colorectal cancer stem cells through epithelial-mesenchymal transition via CDH1 knockdown[J]. Mol Med Rep, 2012, 6(3):507-512.
34. Li J, Zhou BP. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem celllike characters[J]. BMC Cancer, 2011, 11:49.
35. Jin L, Hope KJ, Zhai Q, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells[J]. Nat Med, 2006, 12(10):1167-1174.
36. Gadhoum Z, Delaunay J, Maquarre E, et al. The effect of antiCD44 monoclonal antibodies on differentiation and proliferation of human acute myeloid leukemia cells[J]. Leuk Lymphoma, 2004, 45(8):1501-1510.
37. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis[J]. Nature, 2004, 432(715):324-331.
38. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML[J]. N Engl J Med, 2004, 351(7):657-667.
39. Mamaeva V, Rosenholm JM, Bate-Eya LT, et al. Mesoporous silica nanoparticles as drug delivery systems for targeted inhibition of Notch signaling in cancer[J]. Mol Ther, 2011, 19(8):1538-1546.
40. Clement V, Sanchez P, De Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell selfrenewal, and tumorigenicity[J]. Curr Biol, 2007, 17(2):165-172.
41. Zhou Y, Yang J, Kopeček J. Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells[J]. Biomaterials, 2012, 33(6):1863-1872.

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