• 南京大學(xué)醫(yī)學(xué)院附屬鼓樓醫(yī)院普外科（南京 210008）;

目的 　建立基于人臍靜脈內(nèi)皮細(xì)胞（HUVEC）、纖維蛋白基質(zhì)及微載體的體外三維新生血管模型，在此模型的基礎(chǔ)上，研究CD105在血管新生過(guò)程中的表達(dá)變化及其作用。
方法 　分離、純化并培養(yǎng)HUVEC; 建立三維新生血管模型： 將HUVEC包被于微載體（Cytodex-3）上，然后將該包被有HUVEC的微載體包埋于纖維蛋白凝膠基質(zhì)中，在培養(yǎng)體系中內(nèi)皮細(xì)胞生長(zhǎng)因子的作用下完成HUVEC的出芽、分支、連接成網(wǎng)等過(guò)程。通過(guò)逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)（RT-PCR）檢測(cè)血管新生不同時(shí)期CD105的表達(dá)情況，并利用反義寡核苷酸技術(shù)干預(yù)CD105的表達(dá)，觀察抑制CD105表達(dá)后HUVEC與血管新生過(guò)程的表形變化。
結(jié)果 　包埋于三維纖維蛋白基質(zhì)中的HUVEC出現(xiàn)出芽、分支、連接成網(wǎng)等典型的血管新生過(guò)程； 在此過(guò)程中，CD105的表達(dá)在出芽早期及出芽分支期明顯增強(qiáng)，而在出芽前及成網(wǎng)后的相對(duì)穩(wěn)定期則呈不表達(dá)或弱表達(dá)狀態(tài)。利用反義寡核苷酸抑制CD105表達(dá)后，HUVEC的生長(zhǎng)及新生血管模型中的出芽、分支過(guò)程均受到明顯抑制。
結(jié)論 　CD105在血管新生的不同階段表達(dá)水平不同，在出芽、分支期明顯過(guò)表達(dá)； CD105參與了血管新生過(guò)程，抑制CD105的表達(dá)可以有效地抑制血管新生。

引用本文： 姚永忠,潘一明,孫喜太,仇毓東,丁義濤. 血管新生過(guò)程中CD105的表達(dá)變化及其作用. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(10): 824-829. doi: 復(fù)制

1. Folkman J. What is the evidence that tumors are angiogenesis dependent? [Ｊ]. J Natl Cancer Inst, 1990; 82(1): 4-6.
2. Suh DY. Understanding angiogenesis and its clinical applications [Ｊ]. Ann Clin Lab Sci, 2000; 30(3): 227-238.
3. Sharma S, Sharma MC, Sarkar C. Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis [Ｊ]. Histopathology, 2005; 46(5): 481-489.
4. 駱成玉， 祝學(xué)光. 腫瘤血管生成對(duì)微轉(zhuǎn)移影響的研究進(jìn)展 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2003; 10（5）: 516-518.
5. 張盟輝， 孔憲炳， 王巧玲， 等. 射頻消融聯(lián)合亞砷酸局部治療對(duì)兔肝VX2腫瘤MVD和VEGF表達(dá)的影響 [Ｊ].中國(guó)普外基礎(chǔ)與臨床雜志， 2007; 14（1）： 19-22.
6. Behrem S, Zarkovic K, Eskinja N, et al. Endoglin is a better marker than CD31 in evaluation of angiogenesis in glioblastoma [Ｊ]. Croat Med J, 2005; 46(3): 417-422.
7. Minhajat R, Mori D, Yamasaki F, et al. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers [Ｊ]. Virchows Arch, 2006; 448(2): 127-134.
8. Charpin C, Dales JP, Garcia S, et al. Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays [Ｊ]. Clin Cancer Res, 2004; 10(17): 5815-5819.
9. Yao Y, Pan Y, Chen J, et al. Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF [Ｊ]. Ann Clin Lab Sci, 2007; 37(1): 39-48.
10. Yao Y, Kubota T, Takeuchi H, et al. Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody [Ｊ]. Neuropathology, 2005; 25(3): 201-206.
11. Costello B, Li C, Duff S, et al. Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target [Ｊ]. Int J Cancer, 2004; 109(3): 436-441.
12. Jaffe EA, Nachman RL, Becker CG, et al. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria [Ｊ]. J Clin Invest, 1973; 52(11): 2745-2756.
13. Nehls V, Drenckhahn D. A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis [Ｊ]. Microvasc Res, 1995; 50(3): 311-322.
14. Xue L, Greisler HP. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system [Ｊ]. Surgery, 2002; 132(2): 259-267.
15. Duff SE, Li C, Garland JM, et al. CD105 is important for angiogenesis: evidence and potential applications [Ｊ]. FASEB J, 2003; 17(9): 984-992.
16. Dales JP, Garcia S, Andrac L, et al. Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome [Ｊ]. Int J Oncol, 2004; 24(5): 1197-1204.
17. Wikstrm P, Lissbrant IF, Stattin P, et al. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer [Ｊ]. Prostate, 2002; 51(4): 268-275.
18. 姚衛(wèi)東， 姜惠峰， 曲桂梅, 等. 肝細(xì)胞癌組織中endoglin (CD105)和VEGF 及p57kip2表達(dá)與預(yù)后的關(guān)系 [Ｊ]. 腫瘤防治雜志, 2005; 12(5): 360-364.
19. Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer [Ｊ]. Mod Pathol, 2004; 17(2): 197-203.
20. Saad RS, Jasnosz KM, Tung MY, et al. Endoglin (CD105) expression in endometrial carcinoma [Ｊ]. Int J Gynecol Pathol, 2003; 22(3): 248-253.
21. Saad RS, El-Gohary Y, Memari E, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma [Ｊ]. Hum Pathol, 2005; 36(9): 955-961.
22. 馮立民， 姜希宏， 烏新林, 等. survivin反義寡核苷酸誘導(dǎo)膽囊癌細(xì)胞凋亡的研究 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006; 13(3): 298-301.
23. 車向明， 王曙逢， 樊林, 等. E-cadherin反義寡核苷酸對(duì)腫瘤細(xì)胞浸潤(rùn)能力影響的研究 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006; 13（2）： 191-193.
24. Bartsch M, Weeke-Klimp AH, Meijer DK, et al. Cell-specific targeting of lipid-based carriers for ODN and DNA [Ｊ]. J Liposome Res, 2005; 15(1-2): 59-92.
25. Fonsatti E, Altomonte M, Arslan P, et al. Endoglin (CD105): a target for anti-angiogenetic cancer therapy [Ｊ]. Curr Drug Targets, 2003; 4(4): 291-296.
  1. 1. Folkman J. What is the evidence that tumors are angiogenesis dependent? [Ｊ]. J Natl Cancer Inst, 1990; 82(1): 4-6.
  2. 2. Suh DY. Understanding angiogenesis and its clinical applications [Ｊ]. Ann Clin Lab Sci, 2000; 30(3): 227-238.
  3. 3. Sharma S, Sharma MC, Sarkar C. Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis [Ｊ]. Histopathology, 2005; 46(5): 481-489.
  4. 4. 駱成玉， 祝學(xué)光. 腫瘤血管生成對(duì)微轉(zhuǎn)移影響的研究進(jìn)展 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志， 2003; 10（5）: 516-518.
  5. 5. 張盟輝， 孔憲炳， 王巧玲， 等. 射頻消融聯(lián)合亞砷酸局部治療對(duì)兔肝VX2腫瘤MVD和VEGF表達(dá)的影響 [Ｊ].中國(guó)普外基礎(chǔ)與臨床雜志， 2007; 14（1）： 19-22.
  6. 6. Behrem S, Zarkovic K, Eskinja N, et al. Endoglin is a better marker than CD31 in evaluation of angiogenesis in glioblastoma [Ｊ]. Croat Med J, 2005; 46(3): 417-422.
  7. 7. Minhajat R, Mori D, Yamasaki F, et al. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers [Ｊ]. Virchows Arch, 2006; 448(2): 127-134.
  8. 8. Charpin C, Dales JP, Garcia S, et al. Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays [Ｊ]. Clin Cancer Res, 2004; 10(17): 5815-5819.
  9. 9. Yao Y, Pan Y, Chen J, et al. Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF [Ｊ]. Ann Clin Lab Sci, 2007; 37(1): 39-48.
  10. 10. Yao Y, Kubota T, Takeuchi H, et al. Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody [Ｊ]. Neuropathology, 2005; 25(3): 201-206.
  11. 11. Costello B, Li C, Duff S, et al. Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target [Ｊ]. Int J Cancer, 2004; 109(3): 436-441.
  12. 12. Jaffe EA, Nachman RL, Becker CG, et al. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria [Ｊ]. J Clin Invest, 1973; 52(11): 2745-2756.
  13. 13. Nehls V, Drenckhahn D. A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis [Ｊ]. Microvasc Res, 1995; 50(3): 311-322.
  14. 14. Xue L, Greisler HP. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system [Ｊ]. Surgery, 2002; 132(2): 259-267.
  15. 15. Duff SE, Li C, Garland JM, et al. CD105 is important for angiogenesis: evidence and potential applications [Ｊ]. FASEB J, 2003; 17(9): 984-992.
  16. 16. Dales JP, Garcia S, Andrac L, et al. Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome [Ｊ]. Int J Oncol, 2004; 24(5): 1197-1204.
  17. 17. Wikstrm P, Lissbrant IF, Stattin P, et al. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer [Ｊ]. Prostate, 2002; 51(4): 268-275.
  18. 18. 姚衛(wèi)東， 姜惠峰， 曲桂梅, 等. 肝細(xì)胞癌組織中endoglin (CD105)和VEGF 及p57kip2表達(dá)與預(yù)后的關(guān)系 [Ｊ]. 腫瘤防治雜志, 2005; 12(5): 360-364.
  19. 19. Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer [Ｊ]. Mod Pathol, 2004; 17(2): 197-203.
  20. 20. Saad RS, Jasnosz KM, Tung MY, et al. Endoglin (CD105) expression in endometrial carcinoma [Ｊ]. Int J Gynecol Pathol, 2003; 22(3): 248-253.
  21. 21. Saad RS, El-Gohary Y, Memari E, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma [Ｊ]. Hum Pathol, 2005; 36(9): 955-961.
  22. 22. 馮立民， 姜希宏， 烏新林, 等. survivin反義寡核苷酸誘導(dǎo)膽囊癌細(xì)胞凋亡的研究 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006; 13(3): 298-301.
  23. 23. 車向明， 王曙逢， 樊林, 等. E-cadherin反義寡核苷酸對(duì)腫瘤細(xì)胞浸潤(rùn)能力影響的研究 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006; 13（2）： 191-193.
  24. 24. Bartsch M, Weeke-Klimp AH, Meijer DK, et al. Cell-specific targeting of lipid-based carriers for ODN and DNA [Ｊ]. J Liposome Res, 2005; 15(1-2): 59-92.
  25. 25. Fonsatti E, Altomonte M, Arslan P, et al. Endoglin (CD105): a target for anti-angiogenetic cancer therapy [Ｊ]. Curr Drug Targets, 2003; 4(4): 291-296.