Circulating mouse Flk1+/c-Kit+/CD45- cells function as endothelial progenitors cells (EPCs) and stimulate the growth of human tumor xenografts
详细信息 查看全文
- 作者：Jeffery S Russell (4)
J Martin Brown (5)
4. Head and Neck/Endocrine Oncology ; Moffitt Cancer Center ; 12902 Magnolia Drive ; Tampa ; FL ; 33612 ; USA
5. Division of Radiation and Cancer Biology ; Department of Radiation Oncology ; Stanford University School of Medicine ; 1050A Arastradero Rd. ; Rm A246 ; Palo Alto ; CA ; 94304-1334 ; USA - 关键词：Vasculogenesis ; Endothelial progenitor cell ; Angiogenesis ; Tumor ; Microenvironment ; Therapy ; Resistance
- 刊名：Molecular Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：13
- 期：1
- 全文大小：2,636 KB
- 参考文献：1. Asahara, T, Murohara, T, Sullivan, A, Silver, M, van der Zee, R, Li, T, Witzenbichler, B, Schatteman, G, Isner, JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: pp. 964-967 f="http://dx.doi.org/10.1126/science.275.5302.964" target="_blank" title="It opens in new window">CrossRef
2. Gill, M, Dias, S, Hattori, K, Rivera, ML, Hicklin, D, Witte, L, Girardi, L, Yurt, R, Himel, H, Rafii, S (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+) AC133(+) endothelial precursor cells. Circ Res 88: pp. 167-174 f="http://dx.doi.org/10.1161/01.RES.88.2.167" target="_blank" title="It opens in new window">CrossRef
3. Folkman, J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: pp. 1182-1186 f="http://dx.doi.org/10.1056/NEJM197108122850711" target="_blank" title="It opens in new window">CrossRef
4. Bertolini, F, Shaked, Y, Mancuso, P, Kerbel, RS (2006) The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 6: pp. 835-845 f="http://dx.doi.org/10.1038/nrc1971" target="_blank" title="It opens in new window">CrossRef
5. Resch, T, Pircher, A, Kahler, CM, Pratschke, J, Hilbe, W (2012) Endothelial progenitor cells: current issues on characterization and challenging clinical applications. Stem Cell Rev 8: pp. 926-939 f="http://dx.doi.org/10.1007/s12015-011-9332-9" target="_blank" title="It opens in new window">CrossRef
6. Tepper, OM, Galiano, RD, Capla, JM, Kalka, C, Gagne, PJ, Jacobowitz, GR, Levine, JP, Gurtner, GC (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106: pp. 2781-2786 f="http://dx.doi.org/10.1161/01.CIR.0000039526.42991.93" target="_blank" title="It opens in new window">CrossRef
7. Ince, H, Petzsch, M, Kleine, HD, Eckard, H, Rehders, T, Burska, D, Kische, S, Freund, M, Nienaber, CA (2005) Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial. Circulation 112: pp. I73-I80 f="http://dx.doi.org/10.1161/CIRCULATIONAHA.105.541433" target="_blank" title="It opens in new window">CrossRef
8. Strauer, BE, Brehm, M, Zeus, T, Kostering, M, Hernandez, A, Sorg, RV, Kogler, G, Wernet, P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: pp. 1913-1918 f="http://dx.doi.org/10.1161/01.CIR.0000034046.87607.1C" target="_blank" title="It opens in new window">CrossRef
9. Assmus, B, Schachinger, V, Teupe, C, Britten, M, Lehmann, R, Dobert, N, Grunwald, F, Aicher, A, Urbich, C, Martin, H, Hoelzer, D, Dimmeler, S, Zeiher, AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106: pp. 3009-3017 f="http://dx.doi.org/10.1161/01.CIR.0000043246.74879.CD" target="_blank" title="It opens in new window">CrossRef
10. Tateishi-Yuyama, E, Matsubara, H, Murohara, T, Ikeda, U, Shintani, S, Masaki, H, Amano, K, Kishimoto, Y, Yoshimoto, K, Akashi, H, Shimada, K, Iwasaka, T, Imaizumi, T (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 360: pp. 427-435 f="http://dx.doi.org/10.1016/S0140-6736(02)09670-8" target="_blank" title="It opens in new window">CrossRef
11. Fadini, GP, Avogaro, A, Ferraccioli, G, Agostini, C (2010) Endothelial progenitors in pulmonary hypertension: new pathophysiology and therapeutic implications. Eur Respir J 35: pp. 418-425 f="http://dx.doi.org/10.1183/09031936.00112809" target="_blank" title="It opens in new window">CrossRef
12. Sala, E, Villena, C, Balaguer, C, Rios, A, Fernandez-Palomeque, C, Cosio, BG, Garcia, J, Noguera, A, Agusti, A (2010) Abnormal levels of circulating endothelial progenitor cells during exacerbations of COPD. Lung 188: pp. 331-338 f="http://dx.doi.org/10.1007/s00408-009-9225-8" target="_blank" title="It opens in new window">CrossRef
13. Lyden, D, Hattori, K, Dias, S, Costa, C, Blaikie, P, Butros, L, Chadburn, A, Heissig, B, Marks, W, Witte, L, Wu, Y, Hicklin, D, Zhu, Z, Hackett, NR, Crystal, RG, Moore, MA, Hajjar, KA, Manova, K, Benezra, R, Rafii, S (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7: pp. 1194-1201 f="http://dx.doi.org/10.1038/nm1101-1194" target="_blank" title="It opens in new window">CrossRef
14. Mancuso, P, Burlini, A, Pruneri, G, Goldhirsch, A, Martinelli, G, Bertolini, F (2001) Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 97: pp. 3658-3661 f="http://dx.doi.org/10.1182/blood.V97.11.3658" target="_blank" title="It opens in new window">CrossRef
15. Gao, D, Nolan, DJ, Mellick, AS, Bambino, K, McDonnell, K, Mittal, V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319: pp. 195-198 f="http://dx.doi.org/10.1126/science.1150224" target="_blank" title="It opens in new window">CrossRef
16. Bergers, G, Hanahan, D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8: pp. 592-603 f="http://dx.doi.org/10.1038/nrc2442" target="_blank" title="It opens in new window">CrossRef
17. Shaked, Y, Ciarrocchi, A, Franco, M, Lee, CR, Man, S, Cheung, AM, Hicklin, DJ, Chaplin, D, Foster, FS, Benezra, R, Kerbel, RS (2006) Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science 313: pp. 1785-1787 f="http://dx.doi.org/10.1126/science.1127592" target="_blank" title="It opens in new window">CrossRef
18. Giantonio, BJ, Catalano, PJ, Meropol, NJ, O鈥橠wyer, PJ, Mitchell, EP, Alberts, SR, Schwartz, MA, Benson, AB (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25: pp. 1539-1544 f="http://dx.doi.org/10.1200/JCO.2006.09.6305" target="_blank" title="It opens in new window">CrossRef
19. Allegra, CJ, Yothers, G, O鈥機onnell, MJ, Sharif, S, Petrelli, NJ, Colangelo, LH, Atkins, JN, Seay, TE, Fehrenbacher, L, Goldberg, RM, O'Reilly, S, Chu, L, Azar, CA, Lopa, S, Wolmark, N (2011) Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 29: pp. 11-16 f="http://dx.doi.org/10.1200/JCO.2010.30.0855" target="_blank" title="It opens in new window">CrossRef
20. de Gramont, A, Van Cutsem, E, Schmoll, HJ, Tabernero, J, Clarke, S, Moore, MJ, Cunningham, D, Cartwright, TH, Hecht, JR, Rivera, F, Im, SA, Bodoky, G, Salazar, R, Maindrault-Goebel, F, Shacham-Shmueli, E, Bajetta, E, Makrutzki, M, Shang, A, Andr茅, T, Hoff, PM (2012) Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 13: pp. 1225-1233 f="http://dx.doi.org/10.1016/S1470-2045(12)70509-0" target="_blank" title="It opens in new window">CrossRef
21. Shojaei, F, Wu, X, Malik, AK, Zhong, C, Baldwin, ME, Schanz, S, Fuh, G, Gerber, HP, Ferrara, N (2007) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b鈥?鈥塆r1+ myeloid cells. Nat Biotechnol 25: pp. 911-920 f="http://dx.doi.org/10.1038/nbt1323" target="_blank" title="It opens in new window">CrossRef
22. Lin, Y, Weisdorf, DJ, Solovey, A, Hebbel, RP (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105: pp. 71-77 f="http://dx.doi.org/10.1172/JCI8071" target="_blank" title="It opens in new window">CrossRef
23. Jain, RK, Duda, DG (2003) Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer Cell 3: pp. 515-516 f="http://dx.doi.org/10.1016/S1535-6108(03)00138-7" target="_blank" title="It opens in new window">CrossRef
24. Machein, MR, Renninger, S, de Lima-Hahn, E, Plate, KH (2003) Minor contribution of bone marrow-derived endothelial progenitors to the vascularization of murine gliomas. Brain Pathol 13: pp. 582-597 f="http://dx.doi.org/10.1111/j.1750-3639.2003.tb00487.x" target="_blank" title="It opens in new window">CrossRef
25. Gothert, JR, Gustin, SE, van Eekelen, JA, Schmidt, U, Hall, MA, Jane, SM, Green, AR, Gottgens, B, Izon, DJ, Begley, CG (2004) Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. Blood 104: pp. 1769-1777 f="http://dx.doi.org/10.1182/blood-2003-11-3952" target="_blank" title="It opens in new window">CrossRef
26. Peters, BA, Diaz, LA, Polyak, K, Meszler, L, Romans, K, Guinan, EC, Antin, JH, Myerson, D, Hamilton, SR, Vogelstein, B, Kinzler, KW, Lengauer, C (2005) Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11: pp. 261-262 f="http://dx.doi.org/10.1038/nm1200" target="_blank" title="It opens in new window">CrossRef
27. Pradhan, KR, Mund, JA, Johnson, C, Vik, TA, Ingram, DA, Case, J (2011) Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom 80: pp. 335-338 f="http://dx.doi.org/10.1002/cyto.b.20602" target="_blank" title="It opens in new window">CrossRef
28. Murakami, J, Li, TS, Ueda, K, Tanaka, T, Hamano, K (2009) Inhibition of accelerated tumor growth by blocking the recruitment of mobilized endothelial progenitor cells after chemotherapy. Int J Cancer 124: pp. 1685-1692 f="http://dx.doi.org/10.1002/ijc.24085" target="_blank" title="It opens in new window">CrossRef
29. Purhonen, S, Palm, J, Rossi, D, Kaskenpaa, N, Rajantie, I, Yla-Herttuala, S, Alitalo, K, Weissman, IL, Salven, P (2008) Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth. Proc Natl Acad Sci U S A 105: pp. 6620-6625 f="http://dx.doi.org/10.1073/pnas.0710516105" target="_blank" title="It opens in new window">CrossRef
30. Fang, S, Wei, J, Pentinmikko, N, Leinonen, H, Salven, P (2012) Generation of functional blood vessels from a single c-kit鈥?鈥塧dult vascular endothelial stem cell. PLoS Biol 10: pp. e1001407 f="http://dx.doi.org/10.1371/journal.pbio.1001407" target="_blank" title="It opens in new window">CrossRef
31. Naito, H, Kidoya, H, Sakimoto, S, Wakabayashi, T, Takakura, N (2012) Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels. EMBO J 31: pp. 842-855 f="http://dx.doi.org/10.1038/emboj.2011.465" target="_blank" title="It opens in new window">CrossRef
32. Schmeisser, A, Strasser, RH (2002) Phenotypic overlap between hematopoietic cells with suggested angioblastic potential and vascular endothelial cells. J Hematother Stem Cell Res 11: pp. 69-79 f="http://dx.doi.org/10.1089/152581602753448540" target="_blank" title="It opens in new window">CrossRef
33. Peichev, M, Naiyer, AJ, Pereira, D, Zhu, Z, Lane, WJ, Williams, M, Oz, MC, Hicklin, DJ, Witte, L, Moore, MA, Rafii, S (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95: pp. 952-958
34. Rafii, S, Lyden, D, Benezra, R, Hattori, K, Heissig, B (2002) Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?. Nat Rev Cancer 2: pp. 826-835 f="http://dx.doi.org/10.1038/nrc925" target="_blank" title="It opens in new window">CrossRef
35. Shaked, Y, Bertolini, F, Man, S, Rogers, MS, Cervi, D, Foutz, T, Rawn, K, Voskas, D, Dumont, DJ, Ben-David, Y, Lawler, J, Henkin, J, Huber, J, Hicklin, DJ, D'Amato, RJ, Kerbel, RS (2005) Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7: pp. 101-111
36. Fazel, S, Cimini, M, Chen, L, Li, S, Angoulvant, D, Fedak, P, Verma, S, Weisel, RD, Keating, A, Li, RK (2006) Cardioprotective c-kit鈥?鈥塩ells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 116: pp. 1865-1877 f="http://dx.doi.org/10.1172/JCI27019" target="_blank" title="It opens in new window">CrossRef
37. Furstenberger, G, von Moos, R, Lucas, R, Thurlimann, B, Senn, HJ, Hamacher, J, Boneberg, EM (2006) Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. Br J Cancer 94: pp. 524-531 f="http://dx.doi.org/10.1038/sj.bjc.6602952" target="_blank" title="It opens in new window">CrossRef
38. Shaked, Y, Henke, E, Roodhart, JM, Mancuso, P, Langenberg, MH, Colleoni, M, Daenen, LG, Man, S, Xu, P, Emmenegger, U, Tang, T, Zhu, Z, Witte, L, Strieter, RM, Bertolini, F, Voest, EE, Benezra, R, Kerbel, RS (2008) Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell 14: pp. 263-273 f="http://dx.doi.org/10.1016/j.ccr.2008.08.001" target="_blank" title="It opens in new window">CrossRef
39. De Palma, M, Venneri, MA, Roca, C, Naldini, L (2003) Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 9: pp. 789-795 f="http://dx.doi.org/10.1038/nm871" target="_blank" title="It opens in new window">CrossRef
40. De Palma, M, Venneri, MA, Galli, R, Sergi Sergi, L, Politi, LS, Sampaolesi, M, Naldini, L (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8: pp. 211-226 f="http://dx.doi.org/10.1016/j.ccr.2005.08.002" target="_blank" title="It opens in new window">CrossRef
41. Grenier, G, Scime, A, Le Grand, F, Asakura, A, Perez-Iratxeta, C, Andrade-Navarro, MA, Labosky, PA, Rudnicki, MA (2007) Resident endothelial precursors in muscle, adipose, and dermis contribute to postnatal vasculogenesis. Stem Cells 25: pp. 3101-3110 f="http://dx.doi.org/10.1634/stemcells.2006-0795" target="_blank" title="It opens in new window">CrossRef
42. Zhang, Y, Daquinag, A, Traktuev, DO, Amaya-Manzanares, F, Simmons, PJ, March, KL, Pasqualini, R, Arap, W, Kolonin, MG (2009) White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res 69: pp. 5259-5266 f="http://dx.doi.org/10.1158/0008-5472.CAN-08-3444" target="_blank" title="It opens in new window">CrossRef
43. Martin-Padura, I, Gregato, G, Marighetti, P, Mancuso, P, Calleri, A, Corsini, C, Pruneri, G, Manzotti, M, Lohsiriwat, V, Rietjens, M, Petit, JY, Bertolini, F (2012) The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Res 72: pp. 325-334 f="http://dx.doi.org/10.1158/0008-5472.CAN-11-1739" target="_blank" title="It opens in new window">CrossRef
44. Chute, JP, Saini, AA, Chute, DJ, Wells, MR, Clark, WB, Harlan, DM, Park, J, Stull, MK, Civin, C, Davis, TA (2002) Ex vivo culture with human brain endothelial cells increases the SCID-repopulating capacity of adult human bone marrow. Blood 100: pp. 4433-4439 f="http://dx.doi.org/10.1182/blood-2002-04-1238" target="_blank" title="It opens in new window">CrossRef
45. Chute, JP, Muramoto, G, Fung, J, Oxford, C (2004) Quantitative analysis demonstrates expansion of SCID-repopulating cells and increased engraftment capacity in human cord blood following ex vivo culture with human brain endothelial cells. Stem Cells 22: pp. 202-215 f="http://dx.doi.org/10.1634/stemcells.22-2-202" target="_blank" title="It opens in new window">CrossRef
46. Chute, JP, Muramoto, GG, Fung, J, Oxford, C (2005) Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34鈥?鈥塁D38- cells and SCID-repopulating cells. Blood 105: pp. 576-583 f="http://dx.doi.org/10.1182/blood-2004-04-1467" target="_blank" title="It opens in new window">CrossRef
47. Li, W, Johnson, SA, Shelley, WC, Yoder, MC (2004) Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp Hematol 32: pp. 1226-1237 f="http://dx.doi.org/10.1016/j.exphem.2004.09.001" target="_blank" title="It opens in new window">CrossRef
48. Chute, JP, Muramoto, GG, Salter, AB, Meadows, SK, Rickman, DW, Chen, B, Himburg, HA, Chao, NJ (2007) Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice. Blood 109: pp. 2365-2372 f="http://dx.doi.org/10.1182/blood-2006-05-022640" target="_blank" title="It opens in new window">CrossRef
49. Montfort, MJ, Olivares, CR, Mulcahy, JM, Fleming, WH (2002) Adult blood vessels restore host hematopoiesis following lethal irradiation. Exp Hematol 30: pp. 950-956 f="http://dx.doi.org/10.1016/S0301-472X(02)00813-5" target="_blank" title="It opens in new window">CrossRef
50. Butler, JM, Nolan, DJ, Vertes, EL, Varnum-Finney, B, Kobayashi, H, Hooper, AT, Seandel, M, Shido, K, White, IA, Kobayashi, M, Witte, L, May, C, Shawber, C, Kimura, Y, Kitajewski, J, Rosenwaks, Z, Bernstein, ID, Rafii, S (2010) Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6: pp. 251-264 f="http://dx.doi.org/10.1016/j.stem.2010.02.001" target="_blank" title="It opens in new window">CrossRef
51. He, H, Xu, J, Warren, CM, Duan, D, Li, X, Wu, L, Iruela-Arispe, ML (2012) Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages. Blood 120: pp. 3152-3162 f="http://dx.doi.org/10.1182/blood-2012-04-422758" target="_blank" title="It opens in new window">CrossRef
52. Ruzinova, MB, Schoer, RA, Gerald, W, Egan, JE, Pandolfi, PP, Rafii, S, Manova, K, Mittal, V, Benezra, R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 4: pp. 277-289 f="http://dx.doi.org/10.1016/S1535-6108(03)00240-X" target="_blank" title="It opens in new window">CrossRef
53. Duda, DG, Cohen, KS, Kozin, SV, Perentes, JY, Fukumura, D, Scadden, DT, Jain, RK (2006) Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 107: pp. 2774-2776 f="http://dx.doi.org/10.1182/blood-2005-08-3210" target="_blank" title="It opens in new window">CrossRef
54. Bailey, AS, Willenbring, H, Jiang, S, Anderson, DA, Schroeder, DA, Wong, MH, Grompe, M, Fleming, WH (2006) Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci U S A 103: pp. 13156-13161 f="http://dx.doi.org/10.1073/pnas.0604203103" target="_blank" title="It opens in new window">CrossRef
55. Fehrenbach, ML, Cao, G, Williams, JT, Finklestein, JM, Delisser, HM (2009) Isolation of murine lung endothelial cells. Am J Physiol Lung Cell Mol Physiol 296: pp. L1096-L1103 f="http://dx.doi.org/10.1152/ajplung.90613.2008" target="_blank" title="It opens in new window">CrossRef
56. Spangrude, GJ, Heimfeld, S, Weissman, IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241: pp. 58-62 f="http://dx.doi.org/10.1126/science.2898810" target="_blank" title="It opens in new window">CrossRef
57. Wu, Z, Hofman, FM, Zlokovic, BV (2003) A simple method for isolation and characterization of mouse brain microvascular endothelial cells. J Neurosci Methods 130: pp. 53-63 f="http://dx.doi.org/10.1016/S0165-0270(03)00206-1" target="_blank" title="It opens in new window">CrossRef
58. Bruscia, EM, Ziegler, EC, Price, JE, Weiner, S, Egan, ME, Krause, DS (2006) Engraftment of donor-derived epithelial cells in multiple organs following bone marrow transplantation into newborn mice. Stem Cells 24: pp. 2299-2308 f="http://dx.doi.org/10.1634/stemcells.2006-0166" target="_blank" title="It opens in new window">CrossRef
59. Rajendran, R, Huang, W, Tang, AM, Liang, JM, Choo, S, Reese, T, Hentze, H, van Boxtel, S, Cliffe, A, Rogers, K, Henry, B, Chuang, KH (2014) Early detection of antiangiogenic treatment responses in a mouse xenograft tumor model using quantitative perfusion MRI. Cancer Med 3: pp. 47-60 f="http://dx.doi.org/10.1002/cam4.177" target="_blank" title="It opens in new window">CrossRef
60. Hlatky, L, Hahnfeldt, P, Folkman, J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn鈥檛 tell us. J Natl Cancer Inst 94: pp. 883-893 f="http://dx.doi.org/10.1093/jnci/94.12.883" target="_blank" title="It opens in new window">CrossRef - 刊物主题：Cancer Research; Oncology;
- 出版者：BioMed Central
- ISSN：1476-4598
文摘
Background Endothelial progenitor cells (EPCs) have been demonstrated to have stem-cell like as well as mature endothelial functions. However, controversy remains as to their origins, immunophenotypic markings, and contribution to the tumor vascular network and tumor survival. Methods Flow cytometric analysis and sorting was used to isolate Flk-1+/c-Kit+/CD45- cells. Matrigel and methycellulose assays, flow cytometry, and gene array analyses were performed to characterize several murine EPC cell populations. Human tumor xenografts were used to evaluate the impact of EPCs on tumor growth and vascular development. Results Flk-1+/c-Kit+/CD45- cells were present at low levels in most murine organs with the highest levels in adipose, aorta/vena cava, and lung tissues. Flk-1+/c-Kit+/CD45- cells demonstrated stem cell qualities through colony forming assays and mature endothelial function by expression of CD31, uptake of acLDL, and vascular structure formation in matrigel. High passage EPCs grown in vitro became more differentiated and lost stem-cell markers. EPCs were found to have hemangioblastic properties as demonstrated by the ability to rescue mice given whole body radiation. Systemic injection of EPCs increased the growth of human xenograft tumors and vessel density. Conclusions Flk-1+/C-Kit+/CD45- cells function as endothelial progenitor cells. EPCs are resident in most murine tissue types and localize to human tumor xenografts. Furthermore, the EPC population demonstrates stem-cell and mature endothelial functions and promoted the growth of tumors through enhanced vascular network formation. Given the involvement of EPCs in tumor development, this unique host-derived population may be an additional target to consider for anti-neoplastic therapy.