利用具有特定奈米片段及彈性的生醫材料去除癌症幹細胞

簡易檢索 / 詳目顯示

回結果列表

研究生：	周育瑄 Yu-Hsuan Chou
論文名稱：	利用具有特定奈米片段及彈性的生醫材料去除癌症幹細胞 Depletion of Colon Cancer-Initiating Cells on Biomaterials Having Specific Nanosegments and Elasticity
指導教授：	樋口亞紺 Akon Higuchi
口試委員:
學位類別：	碩士 Master
系所名稱：	工學院 - 化學工程與材料工程學系 Department of Chemical & Materials Engineering
論文出版年：	2014
畢業學年度：	102
語文別：	英文
論文頁數：	88
中文關鍵詞：	癌症幹細胞
外文關鍵詞：	Colon Cancer-Initiating Cells
相關次數：	點閱：14 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

癌症起始細胞或癌症幹細胞（癌幹細胞）表現自我更新的能力，並負責腫瘤生成。癌幹細胞是一種幹細胞會生成腫瘤，並表現出幹細胞特性，例如自我更新和分化為多種細胞類型的能力的幹細胞。癌幹細胞在腫瘤中作為一個獨特的群體，並導致腫瘤生成從而形成復發和轉移。針對癌幹細胞的特殊療法的發展可能提高生存率和癌症患者的生活品質，特別是那些深受腫瘤轉移疾病之苦的患者。研究者提出了許多標記抗體來辨識癌幹細胞，例如：CD29，CD133，Lgr5，Msi-1，ALDH-1等。然而，專一且可信任的標記抗體來辨識大腸癌細胞尚未確定。唯一可靠的方法來識別和量化癌幹細胞是透過觀察動物體內實驗腫瘤的產生。本研究將大腸癌細胞培養在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上，評估癌幹細胞是否增加（純化）或減少（耗竭）。癌幹細胞能透過培養在Pluronic接枝的基底上被耗盡，且於動物體內實驗沒有腫瘤生成，相反地，癌幹細胞會存活在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上，且於動物體內實驗生成腫瘤。此外，本研究亦利用服樂癌注射劑來辨識癌幹細胞，從研究成果發現體外培養與動物體內實驗呈現相同的趨勢。本研究提出一種特殊的生醫材料Pluronic，當大腸癌細胞培養在Pluronic接枝的盤子上可以耗盡癌幹細胞，而癌幹細胞卻可以在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上存活或增加。

Cancer-initiating cells or cancer stem cells (CSCs) exhibit a self-renewing capacity and are responsible for tumor generation. CSCs are stem cells that form tumors and exhibit stem cell properties, such as self-renewal and the ability to differentiate into multiple cell types. It was suggested that CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. The development of specific therapies targeted at CSCs may improve the survival rates and the quality of life of cancer patients, particularly those suffering from metastatic disease. Several markers for colon CSCs have been proposed: CD24, CD29, CD44, CD133, CD166, Lgr5, Muc2, ESA, Msi-1, and ALDH-1. However, specific and reliable surface markers of colon CSCs have not been identified. The only reliable method to identify and quantify CSCs is the observation of tumor generation in the serial xenotransplantation model. In this study, the Colo205 and LoVo colon cancer cell lines and colon cancer cells established from the cells of colon cancer patients (Primary-colon cancer cells 0317) were cultured on ECM (nanosegment)-grafted, oligopeptide (nanosegment)-grafted, and Pluronic (nanosegment)-grafted dishes having different elasticity (100 kPa to 16 MPa elasticity) as well as tissue culture dishes (TCPS, 10GPa elasticity). The oligopeptide-grafted dishes were prepared from polyvinylalcohol-co-itaconic acid (PVA-IA) coating dishes grafted with several nanosegments (KGGPQVTRGDVFTMP [cell-binding domain derived from vitronectin, oligoVN], GGNGEPRGDTYRAY [cell-binding domain from bone sialoprotein, oligoBSP], and GKKQRFRHRNRKG [heparin-binding domain, oligoHBD]). We evaluated whether the CSCs were enhanced (purified) or decreased (depleted) among the colon cancer cells after the colon cancer cells were cultured on ECM-grafted, oligopeptide-grafted, TCPS, or Pluronic-grafted dishes. The ratio of the CSCs was evaluated from the tumor generation of cancer cells in mice that were subcutaneously xenotransplanted into mice. CSCs in colon cancer cells could be selectively depleted from colon cancer cells (Colo205, LoVo, and Primary-colon cancer cells) when they were cultured on Pluronic-grafted dishes having optimal elasticity, whereas CSCs were maintained on TCPS and extracellular matrix (ECM)-immobilized dishes as well as oligopeptide-immobilized dishes. Furthermore, there is no tumor generation of colon cancer cells cultured on pluronic-grafted dishes while there is tumor generation of colon cancer cells cultured on oligopeptide-immobilized dishes. On the other hand, anticancer drug (5-Fluorouracil) was used as well to identify CSCs in colon cancer cells. The results show the same tendency in in vitro cultivation and in vivo experiment. It was concluded that the pluronic-grafted dishes deplete cancer-initiating cells (CSCs) from colon cancer cells while CSCs in colon cancer cells remain or enhance on TCPS and oligopeptide-immobilized dishes, which was explained by specific biomedical characteristics of Pluronic.

Index of Contents

Chapter 1 Introduction    VIII
1-1 The relationship between stem cells and cancer stem cells    1
1-1-1 Stem cells    1
1-1-2 Cancers and cancer stem cells    3
1-1-3 Identity of cancer stem cells    6
1-1-4 Relationship between cancer cells and microenvironment    10
1-1-4-1 ECM    11
1-1-4-2 Purification of cancer stem cells on biomaterials having nano-segment    15
1-2 Sphere-forming assay    17
1-3 Immunofluorescent staining (IF)    18
1-4 In vivo tumorigenic assay    20
Chapter 2 Materials and Methods    21
2-1 Cell lines and patient specimens    21
2-1-1 Cancer cell lines    21
2-1-2 Patient specimen    21
2-2 Cell culture condition    22
2-2-1 LoVo cells    22
2-2-2 Colo205 cells    22
2-2-3 Primary-colon cancer cells    23
2-3 Preparation of chemotherapeutic agents    23
2-4 Preparation of buffer solution    24
2-5 Preparation of CDI activated pluronic Poly-L-lysine plates    24
2-6 Preparation of ECM-grafted Poly(VA-IA) plates    25
2-6-1 Material for PVA-IA film preparation    25
2-6-2 PVA-IA film preparation    25
2-6-3 Preparation of PVA-IA coating plates grafted with ECM and oligopeptide    26
2-7 Sphere-forming assay    27
2-8 In vivo tumor generation    28
2-9 Immunofluorescence    29
Chapter 3 Results and Discussion    32
3-1 The effect of drug treatment on the cell morphology    32
3-1-1 The cell morphology of LoVo colon cancer cells cultivated under drug treatment    32
3-2 The effect of the microenvironment on the cell morphology    33
3-2-1 The cell morphology on Pluronic-immobilized plates    33
3-2-2 The cell morphology on Poly(VA-IA) and ECM-grafted Poly(VA-IA) plates    34
3-3 Characterization of purified cancer stem cells (CSCs)    43
3-3-1 Putative cancer stem cell markers analyzed by immunofluorescence staining    44
3-3-2 The tumorigenic potential of putative cancer stem cells analyzed by sphere-forming assay    45
3-4 In vivo tumorigenic bioassay    60
3-4-1 The tumorigenic potential of putative cancer stem cells sorted by chemotherapy    61
3-4-2 The tumorigenic potential of colon cancer cells cultivated on surface modified plates    61
Chapter 4 Conclusion    64
Supplementary data    66
Reference    67

Index of Figures
FIGURE 1 HSC SYSTEM IS THE FIRST- AND BEST-CHARACTERIZED INTERNS OF HIERARCHICAL ORGANIZATION AND CONSECUTIVE DIFFERENTIATION OF CELLULAR POPULATIONS [9].    3
FIGURE 2 PARALLELS BETWEEN NORMAL STEM CELLS AND CANCER STEM CELLS [10].    5
FIGURE 3 SPECIFIC THERAPY TARGETING THE CANCER STEM CELLS.    10
FIGURE 4 ECM CAN TRIGGER TUMOR CELLS, WHICH SECRETE SEVERAL FACTORS INCLUDING PROTEASES OF MMPS AND PLASMIN THAT DEGRADE ECM FACILITATING THEIR MIGRATION AND INVASION [46].    12
FIGURE 5 REACTION SCHEME FOR THE SYNTHESIS OF CDI-ACTIVATED PLURONIC F68 AND F127 AND IMMOBILIZATION OF CDI-ACTIVATED PLURONIC F68 AND F127 ON POLY-L-LYSINE COATED PLATE [69].    17
FIGURE 6 TWO MAJOR TYPES OF IMMUNOFLUORESCENCE STAINING.    19
(A) DIRECT IMMUNOFLUORESCENCE STAINING, (B) INDIRECT IMMUNOFLUORESCENCE STAINING    19
FIGURE 7 CANCER STEM-LIKE CELLS WERE PURIFIED OR CULTURED ON SEVERAL CONDITIONS.    29
FIGURE 8 THE MORPHOLOGY OF LOVO CELLS TREATED WITH 0.01MM AND 0.001MM 5-FU UNDER 2H, 12H, 24H, 48H, AND 7DAYS OF CULTIVATION.    35
FIGURE 9 THE MORPHOLOGY OF 0317-PRIMARY COLON CANCER CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS PLATES AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    36
FIGURE 10 THE MORPHOLOGY OF COLO205 CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS PLATES AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    37
FIGURE 11 THE MORPHOLOGY OF LOVO CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS PLATES AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    38
FIGURE 12 THE GROWTH CURVE OF 0317-PRIMARY-COLON CANCER CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    39
FIGURE 13 THE GROWTH CURVE OF COLO205 CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    39
FIGURE 14 THE GROWTH CURVE OF LOVO CELLS CULTIVATED ON THE PLURONIC-IMMOBILIZED PLATES (PLL-F68-50 AND PLL-F127-50), TCPS AND PLL0 PLATES DURING 7 DAYS OF CULTIVATION.    40
FIGURE 15 THE MORPHOLOGY OF 0317-PRIMARY-COLON CANCER CELLS, COLO205 CELLS, AND LOVO CELLS CULTIVATED ON POLY(VA-IA) PLATES AFTER 5 DAYS OF CULTIVATION.    41
FIGURE 16 THE MORPHOLOGY OF 0317-PRIMARY-COLON CANCER CELLS, COLO205 CELLS, AND LOVO CELLS CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES AFTER 5 DAYS OF CULTIVATION.    42
FIGURE 17 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH MASASHI-1 (MSI-1) CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    47
FIGURE 18 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH MASASHI-1 (MSI-1) CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    48
FIGURE 19 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH ALDEHYDE DEHYDROGENASE-1 (ALDH-1) CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    49
FIGURE 20 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH ALDEHYDE DEHYDROGENASE-1 (ALDH-1) CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    50
FIGURE 21 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    51
FIGURE 22 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH CD133 CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    52
FIGURE 23 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH CD29 CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    53
FIGURE 24 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH CD29 CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    54
FIGURE 25 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH LGR5 CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    55
FIGURE 26 THE IMMUNOFLUORESCENCE ANALYSIS OF LOVO CELLS STAINED WITH LGR5 CULTIVATED ON ECM-GRAFTED POLY(VA-IA) PLATES.    56
FIGURE 27 SPHERE FORMATION OF LOVO CELLS CULTURED ON ECM-GRAFTED POLY(VA-IA) PLATES THEN SHIFTED TO ULTRA-LOW ATTACHMENT PLATES UNTIL DAY 14.    57
FIGURE 28 SPHERE FORMATION OF LOVO CELLS CULTURED ON ECM-GRAFTED POLY(VA-IA) PLATES THEN SHIFTED TO ULTRA-LOW ATTACHMENT PLATES UNTIL DAY 14.    58
FIGURE 29 SPHERE FORMATION OF LOVO CELLS CULTURED ON PLURONIC-IMMOBILIZED PLATES THEN SHIFTED TO ULTRA-LOW ATTACHMENT PLATES UNTIL DAY 9.    59
FIGURE 30 THE NUMBERS OF SPHERE FORMATION OF LOVO CELLS CULTURED ON SEVERAL CONDITIONS.    59
FIGURE 31 EVALUATION OF TUMORIGENIC POTENTIAL OF LOVO CELLS CULTURED WITH 5-FLUOROURACIL (5-FU) TREATMENT.    63
FIGURE 32 EVALUATION OF TUMORIGENIC POTENTIAL OF LOVO CELLS CULTURED ON SEVERAL CONDITIONS.    63

















Index of Tables
TABLE 1 CANCER STEM CELLS IDENTIFIED AND THEIR SURFACE MARKERS [40].    9
TABLE 2 THE SURFACE MARKER OF COLON CANCER-INITIATING CELLS [28].    9
TABLE 3 TYPES OF COLLAGEN[64].    14
TABLE 4. PRIMARY ANTIBODIES    30
TABLE 5. SECONDARY ANTIBODIES    30
TABLE 6 THE TUMOR VOLUME AFTER INJECTION OF LOVO CELLS UNDER CHEMOTHERAPEUTIC REAGENT TREATMENT INTO BALB/C NUDE FEMALE MICE SUBCUTANEOUSLY.    62
TABLE 7 THE TUMOR VOLUME AFTER INJECTION OF LOVO CELLS UNDER SEVERAL CONDITIONS INTO BALB/C NUDE FEMALE MICE SUBCUTANEOUSLY.    62


                                

Reference
1. Reya, T., et al., Stem cells, cancer, and cancer stem cells. Nature, 2001. 414(6859): p. 105-111.
2. Verfaillie, C.M., M.F. Pera, and P.M. Lansdorp, Stem cells: hype and reality. Hematology Am Soc Hematol Educ Program, 2002: p. 369-91.
3. Guo, W., J.L. Lasky, and H. Wu, Cancer Stem Cells. Pediatric Research, 2006. 59: p. 59R-64R.
4. Morrison, S.J. and I.L. Weissman, The Long-Term Repopulating Subset of Hematopoietic Stem-Cells Is Deterministic and Isolatable by Phenotype. Immunity, 1994. 1(8): p. 661-673.
5. Baum, C.M., et al., Isolation of a Candidate Human Hematopoietic Stem-Cell Population. Proceedings of the National Academy of Sciences of the United States of America, 1992. 89(7): p. 2804-2808.
6. Osawa, M., et al., Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science, 1996. 273(5272): p. 242-245.
7. Clarke, M.F. and M. Fuller, Stem cells and cancer: Two faces of eve. Cell, 2006. 124(6): p. 1111-1115.
8. Dalerba, P., R.W. Cho, and M.F. Clarke, Cancer stem cells: Models and concepts, in Annual Review of Medicine. 2007. p. 267-284.
9. http://www.nature.com/ng/journal/v41/n11/fig_tab/ng1109-1164_F1.html.
10. Pardal, R., M.F. Clarke, and S.J. Morrison, Applying the principles of stem-cell biology to cancer. Nature Reviews Cancer, 2003. 3(12): p. 895-902.
11. Bonnet, D. and J.E. Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 1997. 3(7): p. 730-737.
12. Spira, A. and D.S. Ettinger, Multidisciplinary management of lung cancer - Reply. New England Journal of Medicine, 2004. 350(19): p. 2009-2010.
13. Hsu, H.S., et al., Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSM2 deregulation and is a poor prognostic factor in nonsmoking lung cancer. Clinical Cancer Research, 2005. 11(15): p. 5410-5416.
14. Bernstein, E.D., S.M. Herbert, and N.H. Hanna, Chemotherapy and radiotherapy in the treatment of resectable non-small-cell lung cancer. Annals of Surgical Oncology, 2006. 13(3): p. 291-301.
15. Socinski, M.A. and J.A. Bogart, Limited-stage small-cell lung cancer: The current status of combined-modality therapy. Journal of Clinical Oncology, 2007. 25(26): p. 4137-4145.
16. Chen, Y.-C., et al., Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells. Plos One, 2008. 3(7).
17. Lam, W.K. and D.N. Watkins, Lung cancer: Future directions. Respirology, 2007. 12(4): p. 471-477.
18. Al-Hajj, M., et al., Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 2003. 100(7): p. 3983-3988.
19. Jemal, A., et al., Cancer statistics, 2006. Ca-a Cancer Journal for Clinicians, 2006. 56(2): p. 106-130.
20. Ricci-Vitiani, L., et al., Identification and expansion of human colon-cancer-initiating cells. Nature, 2007. 445(7123): p. 111-115.
21. Goodell, M.A., et al., Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. Journal of Experimental Medicine, 1996. 183(4): p. 1797-1806.
22. Chiasson, B.J., et al., Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. Journal of Neuroscience, 1999. 19(11): p. 4462-4471.
23. Seaberg, R.M. and D. van der Kooy, Stem and progenitor cells: the premature desertion of rigorous definitions. Trends in Neurosciences, 2003. 26(3): p. 125-131.
24. Vermeulen, L., et al., Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proceedings of the National Academy of Sciences of the United States of America, 2008. 105(36): p. 13427-13432.
25. Singh, S.K., et al., Identification of human brain tumour initiating cells. Nature, 2004. 432(7015): p. 396-401.
26. O'Brien, C.A., et al., A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 2007. 445(7123): p. 106-110.
27. Ricci-Vitiani, L., et al., Colon cancer stem cells. Journal of Molecular Medicine-Jmm, 2009. 87(11): p. 1097-1104.
28. Todaro, M., et al., Colon Cancer Stem Cells: Promise of Targeted Therapy. Gastroenterology, 2010. 138(6): p. 2151-2162.
29. Papailiou, J., et al., Stem cells in colon cancer. A new era in cancer theory begins. International Journal of Colorectal Disease, 2011. 26(1): p. 1-11.
30. Yin, A.H., et al., AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood, 1997. 90(12): p. 5002-5012.
31. Hilbe, W., et al., CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer. Journal of Clinical Pathology, 2004. 57(9): p. 965-969.
32. Eramo, A., et al., Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death and Differentiation, 2008. 15(3): p. 504-514.
33. Barker, N., et al., Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature, 2007. 449(7165): p. 1003-U1.
34. Haegebarth, A. and H. Clevers, Wnt Signaling, Lgr5, and Stem Cells in the Intestine and Skin. American Journal of Pathology, 2009. 174(3): p. 715-721.
35. Walker, F., et al., LGR5 Is a Negative Regulator of Tumourigenicity, Antagonizes Wnt Signalling and Regulates Cell Adhesion in Colorectal Cancer Cell Lines. Plos One, 2011. 6(7).
36. Kaneko, Y., et al., Musashi1: An evolutionally conserved marker for CNS progenitor cells including neural stem cells. Developmental Neuroscience, 2000. 22(1-2): p. 139-153.
37. Booth, C. and C.S. Potten, Gut instincts: thoughts on intestinal epithelial stem cells. Journal of Clinical Investigation, 2000. 105(11): p. 1493-1499.
38. Nishimura, S., et al., Expression of Musashi-1 in human normal colon crypt cells - A possible stem cell marker of human colon epithelium. Digestive Diseases and Sciences, 2003. 48(8): p. 1523-1529.
39. Huang, E.H., et al., Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis. Cancer Research, 2009. 69(8): p. 3382-3389.
40. Klonisch, T., et al., Cancer stem cell markers in common cancers - therapeutic implications. Trends in Molecular Medicine, 2008. 14(10): p. 450-460.
41. Joyce, J.A. and J.W. Pollard, Microenvironmental regulation of metastasis. Nature Reviews Cancer, 2009. 9(4): p. 239-252.
42. Armstrong, T., et al., Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Clinical Cancer Research, 2004. 10(21): p. 7427-7437.
43. Hurt, E.M., et al., Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation. Stem Cells, 2010. 28(3): p. 390-398.
44. Dityatev, A. and M. Schachner, Extracellular matrix molecules and synaptic plasticity. Nature Reviews Neuroscience, 2003. 4(6): p. 456-468.
45. Wall, S.J., et al., Meeting report: Proteases, extracellular matrix, and cancer: an AACR Special Conference in Cancer Research. Cancer Res, 2003. 63(15): p. 4750-5.
46. Dasgupta, S., S. Srinidhi, and J.K. Vishwanatha, Oncogenic activation in prostate cancer progression and metastasis: Molecular insights and future challenges. J Carcinog, 2012. 11: p. 4.
47. Giancotti, F.G. and E. Ruoslahti, Transduction - Integrin signaling. Science, 1999. 285(5430): p. 1028-1032.
48. Hood, J.D. and D.A. Cheresh, Role of integrins in cell invasion and migration. Nature Reviews Cancer, 2002. 2(2): p. 91-+.
49. Lee, J.W. and R. Juliano, Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. Molecules and Cells, 2004. 17(2): p. 188-202.
50. Sethi, T., et al., Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: A mechanism for small cell lung cancer growth and drug resistance in vivo. Nature Medicine, 1999. 5(6): p. 662-668.
51. Damiano, J.S., et al., Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines. Blood, 1999. 93(5): p. 1658-1667.
52. Uhm, J.H., et al., Vitronectin, a glioma-derived extracellular matrix protein, protects tumor cells from apoptotic death. Clinical Cancer Research, 1999. 5(6): p. 1587-1594.
53. Aoudjit, F. and K. Vuori, Integrin signaling in cancer cell survival and chemoresistance. Chemother Res Pract, 2012. 2012: p. 283181.
54. Jinka, R., et al., Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers. International Journal of Cell Biology, 2012. 2012: p. 1-8.
55. Weiss, R.E. and A.H. Reddi, Synthesis and localization of fibronectin during collagenous matrix-mesenchymal cell interaction and differentiation of cartilage and bone in vivo. Proc Natl Acad Sci U S A, 1980. 77(4): p. 2074-8.
56. Kim, S., et al., The effect of fibronectin-coated implant on canine osseointegration. J Periodontal Implant Sci, 2011. 41(5): p. 242-7.
57. Norton, P.A. and R.O. Hynes, In vitro splicing of fibronectin pre-mRNAs. Nucleic Acids Res, 1990. 18(14): p. 4089-97.
58. Han, S.W., F.R. Khuri, and J. Roman, Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways. Cancer Research, 2006. 66(1): p. 315-323.
59. http://en.wikipedia.org/wiki/Main_Page.
60. Preissner, K.T. and D. Seiffert, Role of vitronectin and its receptors in haemostasis and vascular remodeling. Thrombosis Research, 1998. 89(1): p. 1-21.
61. Habermann, B.F. and D.A. Cheresh, Vitronectin and its receptors. Current Opinion in Cell Biology, 1993. 5(5): p. 864-868.
62. Di Lullo, G.A., et al., Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. Journal of Biological Chemistry, 2002. 277(6): p. 4223-4231.
63. Mollenhauer, J., I. Roether, and H.F. Kern, Distribution of extracellular matrix proteins in pancreatic ductal adenocarcinoma and its influence on tumor cell proliferation in vitro. Pancreas, 1987. 2(1): p. 14-24.
64. http://themedicalbiochemistrypage.org/extracellularmatrix.html.
65. Kleinman, H.K. and G.R. Martin, Matrigel: Basement membrane matrix with biological activity. Seminars in Cancer Biology, 2005. 15(5): p. 378-386.
66. Higuchi, A., et al., Bioinert surface of pluronic-immobilized flask for preservation of hematopoietic stem cells. Biomacromolecules, 2006. 7(4): p. 1083-1089.
67. Higuchi, A., et al., Temperature-induced cell detachment on immobilized pluronic surface. Journal of Biomedical Materials Research Part A, 2006. 79A(2): p. 380-392.
68. Ungefroren, H., et al., Interaction of tumor cells with the microenvironment. Cell Communication and Signaling, 2011. 9.
69. Higuchi, A., et al., Preservation of hematopoietic stem and progenitor cells from umbilical cord blood stored in a surface derivatized with polymer nanosegments. Biomacromolecules, 2008. 9(2): p. 634-639.
70. Todaro, M., et al., Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell, 2007. 1(4): p. 389-402.
71. Ieta, K., et al., Biological and genetic characteristics of tumor-initiating cells in colon cancer. Annals of Surgical Oncology, 2008. 15(2): p. 638-648.
72. von dem Borne, A.E., et al., A simple immunofluorescence test for the detection of platelet antibodies. Br J Haematol, 1978. 39(2): p. 195-207.
73. Collins, A.T., et al., Prospective identification of tumorigenic prostate cancer stem cells. Cancer Research, 2005. 65(23): p. 10946-10951.
74. Welte, Y., et al., Cancer stem cells in solid tumors: elusive or illusive? Cell Communication and Signaling, 2010. 8.
75. Bao, S.D., et al., Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Research, 2006. 66(16): p. 7843-7848.
76. Bruno, S., et al., CD133(+) renal progenitor cells contribute to tumor angiogenesis. American Journal of Pathology, 2006. 169(6): p. 2223-2235.
77. Yoshikawa, R., et al., Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy. British Journal of Cancer, 2008. 98(10): p. 1670-1674.
78. Zhu, L.Q., et al., Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature, 2009. 457(7229): p. 603-U114.
79. Shmelkov, S.V., et al., CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest, 2008. 118(6): p. 2111-20.
80. Yang, Z.F., et al., Identification of local and circulating cancer stem cells in human liver cancer. Hepatology, 2008. 47(3): p. 919-928.
81. Dittfeld, C., et al., CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell line HCT-116. Radiotherapy and Oncology, 2010. 94(3): p. 375-383.
82. Gupta, P.B., C.L. Chaffer, and R.A. Weinberg, Cancer stem cells: mirage or reality? Nat Med, 2009. 15(9): p. 1010-2.
83. Lo, P.K., et al., CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFbeta signaling. Oncogene, 2012. 31(21): p. 2614-26.
84. Lee, H.C., et al., Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells. Drug Des Devel Ther, 2013. 7: p. 491-502.
85. Higuchi, A., et al., Biomimetic Cell Culture Proteins as Extracellular Matrices for Stem Cell Differentiation. Chemical Reviews, 2012. 112(8): p. 4507-4540.
86. Visvader, J.E. and G.J. Lindeman, Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer, 2008. 8(10): p. 755-68.
87. Kao, T.C., et al., Suppression of cancer-initiating cells and selection of adipose-derived stem cells cultured on biomaterials having specific nanosegments. J Biomed Mater Res B Appl Biomater, 2014. 102(3): p. 463-76.

簡易檢索 / 詳目顯示

相關論文