Expression and Function of CD105 in Angiogenesis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YAO Yongzhong , PAN Yiming , SUN Xitai , QIU Yudong , DING Yitao.

Department of General Surgery, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, ChinaCorresponding Author: DING Yi-tao， E-mail： dingyitaonj@hotmail.com;

Corresponding author：

Keywords：

Angiogenesis; Human umbilical vein endothelial cell; CD105; Three-dimensional angiogenesis system; Microcarrier

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Objective 　To develop an in vitro three-dimensional angiogenesis system and analyze the expression and function of CD105 in angiogenesis.
Methods 　After primary human umbilical vein endothelial cells (HUVEC) were purified and cultured, the microcarriers were coated with HUVEC and then embedded and cultured into fibrin gel. The angiogenesis process of HUVEC on the microcarriers was formed. The expression of CD105 during this process was detected by reverse transcription polymerase chain reaction (RT-PCR). Antisense oligodeoxynucleotide (ASODN) was used to inhibit the expression of CD105 and the changes of the angiogenesis process were analyzed quantitatively.
Results 　HUVEC on the microcarriers which were embedded into the fibrin gel, occurred the angiogenesis process of sprouts, branches and capillary networks with lumina. During this process, CD105 was over expressed in the periods of forming sprouts and branches, and depressed in the relatively steady periods including the periods before forming sprouts and after forming capillary networks. While the expression of CD105 was inhibited by ASODN, the angiogenesis process was significantly inhibited.
Conclusions 　The expression of CD105 is varied within the angiogenesis process, over expressing during the sprouts and branches forming periods. Inhibiting the expression of CD105 could efficiently inhibit angiogenesis.

Citation： YAO Yongzhong,PAN Yiming,SUN Xitai,QIU Yudong,DING Yitao.. Expression and Function of CD105 in Angiogenesis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(10): 824-829. doi: Copy

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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.	骆成玉，祝学光. 肿瘤血管生成对微转移影响的研究进展 [Ｊ]. 中国普外基础与临床杂志， 2003; 10（5）: 516-518.
5.	张盟辉，孔宪炳，王巧玲，等. 射频消融联合亚砷酸局部治疗对兔肝VX2肿瘤MVD和VEGF表达的影响 [Ｊ].中国普外基础与临床杂志， 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.	姚卫东，姜惠峰，曲桂梅, 等. 肝细胞癌组织中endoglin (CD105)和VEGF 及p57kip2表达与预后的关系 [Ｊ]. 肿瘤防治杂志, 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.	冯立民，姜希宏，乌新林, 等. survivin反义寡核苷酸诱导胆囊癌细胞凋亡的研究 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(3): 298-301.
23.	车向明，王曙逢，樊林, 等. E-cadherin反义寡核苷酸对肿瘤细胞浸润能力影响的研究 [Ｊ]. 中国普外基础与临床杂志, 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. 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. 骆成玉，祝学光. 肿瘤血管生成对微转移影响的研究进展 [Ｊ]. 中国普外基础与临床杂志， 2003; 10（5）: 516-518.
5. 张盟辉，孔宪炳，王巧玲，等. 射频消融联合亚砷酸局部治疗对兔肝VX2肿瘤MVD和VEGF表达的影响 [Ｊ].中国普外基础与临床杂志， 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. 姚卫东，姜惠峰，曲桂梅, 等. 肝细胞癌组织中endoglin (CD105)和VEGF 及p57kip2表达与预后的关系 [Ｊ]. 肿瘤防治杂志, 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. 冯立民，姜希宏，乌新林, 等. survivin反义寡核苷酸诱导胆囊癌细胞凋亡的研究 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(3): 298-301.
23. 车向明，王曙逢，樊林, 等. E-cadherin反义寡核苷酸对肿瘤细胞浸润能力影响的研究 [Ｊ]. 中国普外基础与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and Function of CD105 in Angiogenesis

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