胃癌组织Angiopoietin-2及MMP-9表达的意义
钱颉,华中科技大学同济医学院附属同济医院消化内科
湖北省武汉市 430030
刘南植,程胜平, 华中科技大学同济医学院附属同济医院肝病研究所
湖北省武汉市 430030
项目负责人:钱颉, 430030, 湖北省武汉市汉口解放大道1095号, 华中科技大学同济医学院附属同济医院消化内科. xuer_qian@163.com
电话:027-83645986
收稿日期:2004-09-22 接受日期: 2004-10-11
, http://www.100md.com
Expression of Angiopoietin-2 and Matrixmetalloproteinase-9 in gastric carcinoma
Jie Qian, Nan-Zhi Liu, Sheng-Ping Cheng
Jie Qian, Department of Digestive Diseases, Affiliated Tongji Hospital of TongjiMedical College, Huazhong University of Science and Technology, Wuhan430030, Hubei Province, China
Nan-Zhi Liu, Sheng-Ping Cheng, Institute of Live Diseases,Affiliated Tongji Hospital of Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan 430030, Hubei Province, China
, 百拇医药
Correspondence to: Jie Qian, Institute of Liver Diseases,Affiliated Tongji Hospital of Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan 430030, Hubei Province, China. xuer_qian@163.com
Received: 2004-09-22 Accepted:2004-10-11
Abstract
AIM: To investigate the expression of angiopoietin-2 (Ang-2) andmatrix metalloproteinase-9 (MMP-9) in gastric carcinoma.
, 百拇医药
METHODS: The expression of Ang-2 and MMP-9 was detected in tissuesof gastric cancer (n = 50) and non-cancerous gastric mucosa (n= 10) by immunohistochemistry.
RESULTS: The positive rates of Ang-2 and MMP-9 in gastric cancerwere 56% and 60%, which were significantly higher than those innon-cancerous mucosa. The level of Ang-2 and MMP-9 expression had anegative correlation with the differentiation degree (25% vs 71%, c2 = 9.18, P<0.01;31% vs 74%, c2 = 8.10, P<0.01), but a positive correlationwith TNM stage (30% vs 78%, P<0.01; 35% vs 81%, P<0.01),lymphatic metastasis (39% vs 70%, P<0.05; 43% vs74%, P<0.05), or microvascular density (Ang-2: 74.9±11.8 vs65.6±11.5, P<0.05). In addition, the level of MMP-9 expressionwas correlated with the invasion depth (33% vs 79%, P<0.01). Also, there was asignificant correlation between the expression of Ang-2 and MMP-9 (c2 = 13.0, P<0.01).
, 百拇医药
CONCLUSION: Ang-2 and MMP-9 playa synergistic role in the invasion and metastasis of gastric carcinoma.Their colocalization may be a useful indicator for the prognosis of thedisease.
Key Words: Angiopoietin-2; Matrix metalloproteinase-9; Gastriccarcinoma; Immunohistochemistry
Qian J, Liu NZ, Cheng SP. Expression of Angiopoietin-2 and Matrixmetalloproteinase-9 in gastric carcinoma. Shijie Huaren Xiaohua Zazhi 2005;13(3):299-302
, http://www.100md.com
摘要
目的:观察血管生成素-2(angiopoietin-2)和金属基质蛋白酶-9(MMP-9)在胃癌组织中的表达,并探讨其临床意义.
方法:用免疫组化染色法检测了50例胃癌患者癌组织,10例非癌胃黏膜组织中angiopoietin-2(Ang-2),MMP-9, CD-34蛋白的表达.
结果:胃癌组织中Ang-2,MMP-9的阳性率分别为56%和60%, 显著高于非癌胃黏膜.他们的表达水平与胃癌的分化程度呈负相关(25%vs 71%, c2= 9.18, P<0.01;31%vs 74%, c2= 8.10, P<0.01), 与肿瘤的TNM分期(30% vs 78%,P<0.01; 35% vs 81%, P<0.01), 淋巴结转移(39%vs 70%, P<0.05; 43% vs 74%, P<0.05), 微血管密度(Ang-2:74.9±11.8vs 65.6±11.5,P<0.05)成正相关(此外,MMP-9的表达水平还与肿瘤浸润的深度成正相关(33%vs 79%, c2= 10.73, P<0.01).Ang-2、MMP-9在胃癌中的阳性表达率之间存在一定相关性(c2= 3.0, P <0.01).
, http://www.100md.com
结论:Ang-2、MMP-9在胃癌的侵袭与转移中起重要作用,并且他们之间存在相互诱导或是协同效应,其共位表达可作为判断预后的指标.
关键词:血管生成素-2;金属基质蛋白酶-9;胃癌;免疫组化
钱颉,刘南植, 程胜平.胃癌组织Angiopoietin-2及MMP-9表达的意义.世界华人消化杂志 2005;13(3):299-302
Asahara T, Chen DH, Takahashi T, Fujikawa K, Kearney M, Magner M,Yancopoulos GD, Isner JM. Tie2 receptor
ligands, angiopoietin-1 and angiopoietin-2,modulate VEGF-Induced postnatal neovascularization.
, 百拇医药
Circulation Research 1998;83:233-240
2 Ferrara N.Vascular endothelial growth factor:molecular and biological aspects. CurrTop Micobiol Immunol 1999;237:1-30
3 Huang XL,Takakura N, Suda T. In vitro effects of angiopoietins and VEGF onhematopoietic and endothelial cells.
Biochem Biophys Res Commun 1999;264:133-138
4 Mezquita J,Mezquita P, Montserrat P, Mezquita B, Francone V, Vilagrasa X, Mezquita C.Genomic structure and
, http://www.100md.com
alternative splicing of chickenangiopoietin-2. Biochem Biophys Res Commun 2000;275:643-651
5 Horner A, BordS, Kelsall AW, Coleman N, Compston JE. Tie2 ligands angiopoietin-1 andangiopoietin-2 are
coexpressed with vascular endothelial cellgrowth factor in growing human bone. Bone 2001;28:65-71
6 Kampfer H,Pfeilschifter J, Frank S. Expressional regulation of angiopoietin-1 and -2and the tie-1 and -2 receptor
, http://www.100md.com
tyrosine kinases during cutaneous woundhealing:a comparative study of normal and impaired repair. Lab Invest
2001;81:361-373
7 Sato T, El-AssalON, Ono T, Yamanoi A, Dhar DK, Nagasue N. Sinusoidal endothelial cellproliferation and expression
of angiopoietin/Tie family in regeneratingrat liver. J Hepatol 2001;34:690-698
8 TscheudschilsurenG, Aust G, Nieber K, Schilling N, Spanel-Borowski K. Microvascularendothelial cells differ in basal
, 百拇医药
and hypoxia-regulated expression ofangiogenic factors and their receptors. Microvasc Res 2002;63:243-251
9 Hu B, Guo P,Fang Q, Tao HQ, Wang D, Nagane M, Huang HJ, Gunji Y, Nishikawa R, AlitaloK, Cavenee WK, Cheng SY.
Angiopoietin-2 induces human gliomainvasion through the activation of matrix metalloprotease-2.
Proc Natl Acad Sci USA 2003;100:8904-8909
10 Das A, FanslowW, Cerretti D, Warren E, Talarico N, McGuire P. Angiopoietin/Tekinteractions regulate mmp-9
, 百拇医药
expression and retinalneovascularization. Lab Invest 2003;83:1637-1645
11 Weidner N,Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, GaspariniG. Tumor angiogenesis:
a new significant and independentprognostic indicator in early-stage breast carcinoma. J Natl CancerInst
1992;84:1875-1887
12 高国林,杨原, 杨思凤, 任彩文.血管内皮细胞增生是胃癌相关性病变. 世界华人消化杂志 2000;8:282-284
, 百拇医药
13 Gasparini G. Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 2000;5:37-44
14 吴静, 樊代明. 肿瘤血管生成与肿瘤血管抑制治疗. 世界华人消化杂志 2001;9:316-321
15 陶厚权,邹寿椿, 王瑞年, 林言箴.血管生成与胃癌发生之间关系的实验研究.世界华人消化杂志
2003;11:43-46
16 Chen L, Yang Z, Wang G, Wang C. Expression of angiopoietin-2 gene and its receptor Tie2 in hepatocellular carcinoma.
, http://www.100md.com
J Tongji Med Univ 2001;21:228-230
17 Currie MJ, Gunningham SP, Turner K, Han C, Scott PA, Robinson BA, Chong W, Harris AL, Fox SB. Expression of
the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas;regulation by the von Hippel-Lindau
gene and hypoxia. J Pathol 2002;198:502-510
18 Gale NW, Thurston G, Davis S, Wiegand SJ, Holash J, Rudge JS, Yancopoulos GD. Complementary and coordinated
, 百拇医药
roles of the VEGFs and angiopoietins during normal and pathologic vascular formation. Cold Spring Harb Symp
Quant Biol 2002;67:267-273
19 Xing L, Zhang Z, Xu Y. Expression of angiopoietin-2 gene in non-small cell lung cancer. J Huazhong Univ Sci
Technolog Med Sci 2003;23:362-364
20 Caine GJ, Blann AD, Stonelake PS, Stonelake PS, Ryan P, Lip GY. Plasma angiopoietin-1, angiopoietin-2 and Tie-2
, 百拇医药
in breast andprostate cancer:a comparison with VEGF and Flt-1. Eur J Clin Invest 2003;33:883-890
21 李楠,徐采朴, 宋波, 房殿春,杨仕明, 门荣莆.人胃癌组织中金属蛋白酶类基因的过度表达.
华人消化杂志 1998;6:118-120
22 洪照友,俞金龙, 张云生, 高毅.基质金属蛋白酶-9, CD34的表达与肝癌侵袭转移的关系.
世界华人消化杂志 2001;9:170-174
23 Kabashima A, Yao T, Sugimachi K, Tsuneyoshi M. Relationship between biologic behavior and phenotypic expression
, 百拇医药
in intramucosal gastric carcinomas. Hum Pathol 2002;33:80-86
24 Wroblewski LE, Pritchard DM, Carter S, Varro A. Gastrin-stimulated gastric epithelial cell invasion:the role and
mechanism of increased matrix metalloproteinase 9 expression. Biochem J 2002;365:873-879
25 Caudroy S, Polette M, Nawrocki-Raby B, Cao J, Toole BP, Zucker S, Birembaut P. EMMPRIN-mediated MMP regulation
, 百拇医药
in tumor and endothelial cells. Clin Exp Metastasis 2002;19:697-702
26 Shin EY, Ma EK, Kim CK, Kwak SJ, Kim EG. Src/ERK but not phospholipase D is involved in keratinocyte growth
factor-stimulated secretion of matrix metalloprotease-9 and urokinase-type plasminogen activator in SNU-16
human stomach cancer cell. J Cancer Res Clin Oncol 2002;128:596-602
27 Nyberg P, Moilanen M, Paju A, Sarin A, Stenman UH, Sorsa T, Salo T. MMP-9 activation by tumor trypsin-2 enhances
, http://www.100md.com
in vivo invasion of human tongue carcinoma cells. J Dent Res 2002;81:831-835
28 Albo D, Shinohara T, Tuszynski GP. Up-regulation of matrix metalloproteinase 9 by thrombospondin 1 in gastric cancer.
J Surg Res 2002;108:51-60
29 郑伟达,王小众. 基质金属蛋白酶及其抑制物与实验性肝纤维化.世界华人消化杂志 2004;12:428-431
30 Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in
gastriccarcinoma:possible in vivo regulation via induction of proteases. CancerRes 2001;61:2145-2153
编辑 潘伯荣 审读 张海宁, http://www.100md.com( 钱 颉, 刘南植, 程胜平)
湖北省武汉市 430030
刘南植,程胜平, 华中科技大学同济医学院附属同济医院肝病研究所
湖北省武汉市 430030
项目负责人:钱颉, 430030, 湖北省武汉市汉口解放大道1095号, 华中科技大学同济医学院附属同济医院消化内科. xuer_qian@163.com
电话:027-83645986
收稿日期:2004-09-22 接受日期: 2004-10-11
, http://www.100md.com
Expression of Angiopoietin-2 and Matrixmetalloproteinase-9 in gastric carcinoma
Jie Qian, Nan-Zhi Liu, Sheng-Ping Cheng
Jie Qian, Department of Digestive Diseases, Affiliated Tongji Hospital of TongjiMedical College, Huazhong University of Science and Technology, Wuhan430030, Hubei Province, China
Nan-Zhi Liu, Sheng-Ping Cheng, Institute of Live Diseases,Affiliated Tongji Hospital of Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan 430030, Hubei Province, China
, 百拇医药
Correspondence to: Jie Qian, Institute of Liver Diseases,Affiliated Tongji Hospital of Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan 430030, Hubei Province, China. xuer_qian@163.com
Received: 2004-09-22 Accepted:2004-10-11
Abstract
AIM: To investigate the expression of angiopoietin-2 (Ang-2) andmatrix metalloproteinase-9 (MMP-9) in gastric carcinoma.
, 百拇医药
METHODS: The expression of Ang-2 and MMP-9 was detected in tissuesof gastric cancer (n = 50) and non-cancerous gastric mucosa (n= 10) by immunohistochemistry.
RESULTS: The positive rates of Ang-2 and MMP-9 in gastric cancerwere 56% and 60%, which were significantly higher than those innon-cancerous mucosa. The level of Ang-2 and MMP-9 expression had anegative correlation with the differentiation degree (25% vs 71%, c2 = 9.18, P<0.01;31% vs 74%, c2 = 8.10, P<0.01), but a positive correlationwith TNM stage (30% vs 78%, P<0.01; 35% vs 81%, P<0.01),lymphatic metastasis (39% vs 70%, P<0.05; 43% vs74%, P<0.05), or microvascular density (Ang-2: 74.9±11.8 vs65.6±11.5, P<0.05). In addition, the level of MMP-9 expressionwas correlated with the invasion depth (33% vs 79%, P<0.01). Also, there was asignificant correlation between the expression of Ang-2 and MMP-9 (c2 = 13.0, P<0.01).
, 百拇医药
CONCLUSION: Ang-2 and MMP-9 playa synergistic role in the invasion and metastasis of gastric carcinoma.Their colocalization may be a useful indicator for the prognosis of thedisease.
Key Words: Angiopoietin-2; Matrix metalloproteinase-9; Gastriccarcinoma; Immunohistochemistry
Qian J, Liu NZ, Cheng SP. Expression of Angiopoietin-2 and Matrixmetalloproteinase-9 in gastric carcinoma. Shijie Huaren Xiaohua Zazhi 2005;13(3):299-302
, http://www.100md.com
摘要
目的:观察血管生成素-2(angiopoietin-2)和金属基质蛋白酶-9(MMP-9)在胃癌组织中的表达,并探讨其临床意义.
方法:用免疫组化染色法检测了50例胃癌患者癌组织,10例非癌胃黏膜组织中angiopoietin-2(Ang-2),MMP-9, CD-34蛋白的表达.
结果:胃癌组织中Ang-2,MMP-9的阳性率分别为56%和60%, 显著高于非癌胃黏膜.他们的表达水平与胃癌的分化程度呈负相关(25%vs 71%, c2= 9.18, P<0.01;31%vs 74%, c2= 8.10, P<0.01), 与肿瘤的TNM分期(30% vs 78%,P<0.01; 35% vs 81%, P<0.01), 淋巴结转移(39%vs 70%, P<0.05; 43% vs 74%, P<0.05), 微血管密度(Ang-2:74.9±11.8vs 65.6±11.5,P<0.05)成正相关(此外,MMP-9的表达水平还与肿瘤浸润的深度成正相关(33%vs 79%, c2= 10.73, P<0.01).Ang-2、MMP-9在胃癌中的阳性表达率之间存在一定相关性(c2= 3.0, P <0.01).
, http://www.100md.com
结论:Ang-2、MMP-9在胃癌的侵袭与转移中起重要作用,并且他们之间存在相互诱导或是协同效应,其共位表达可作为判断预后的指标.
关键词:血管生成素-2;金属基质蛋白酶-9;胃癌;免疫组化
钱颉,刘南植, 程胜平.胃癌组织Angiopoietin-2及MMP-9表达的意义.世界华人消化杂志 2005;13(3):299-302
Asahara T, Chen DH, Takahashi T, Fujikawa K, Kearney M, Magner M,Yancopoulos GD, Isner JM. Tie2 receptor
ligands, angiopoietin-1 and angiopoietin-2,modulate VEGF-Induced postnatal neovascularization.
, 百拇医药
Circulation Research 1998;83:233-240
2 Ferrara N.Vascular endothelial growth factor:molecular and biological aspects. CurrTop Micobiol Immunol 1999;237:1-30
3 Huang XL,Takakura N, Suda T. In vitro effects of angiopoietins and VEGF onhematopoietic and endothelial cells.
Biochem Biophys Res Commun 1999;264:133-138
4 Mezquita J,Mezquita P, Montserrat P, Mezquita B, Francone V, Vilagrasa X, Mezquita C.Genomic structure and
, http://www.100md.com
alternative splicing of chickenangiopoietin-2. Biochem Biophys Res Commun 2000;275:643-651
5 Horner A, BordS, Kelsall AW, Coleman N, Compston JE. Tie2 ligands angiopoietin-1 andangiopoietin-2 are
coexpressed with vascular endothelial cellgrowth factor in growing human bone. Bone 2001;28:65-71
6 Kampfer H,Pfeilschifter J, Frank S. Expressional regulation of angiopoietin-1 and -2and the tie-1 and -2 receptor
, http://www.100md.com
tyrosine kinases during cutaneous woundhealing:a comparative study of normal and impaired repair. Lab Invest
2001;81:361-373
7 Sato T, El-AssalON, Ono T, Yamanoi A, Dhar DK, Nagasue N. Sinusoidal endothelial cellproliferation and expression
of angiopoietin/Tie family in regeneratingrat liver. J Hepatol 2001;34:690-698
8 TscheudschilsurenG, Aust G, Nieber K, Schilling N, Spanel-Borowski K. Microvascularendothelial cells differ in basal
, 百拇医药
and hypoxia-regulated expression ofangiogenic factors and their receptors. Microvasc Res 2002;63:243-251
9 Hu B, Guo P,Fang Q, Tao HQ, Wang D, Nagane M, Huang HJ, Gunji Y, Nishikawa R, AlitaloK, Cavenee WK, Cheng SY.
Angiopoietin-2 induces human gliomainvasion through the activation of matrix metalloprotease-2.
Proc Natl Acad Sci USA 2003;100:8904-8909
10 Das A, FanslowW, Cerretti D, Warren E, Talarico N, McGuire P. Angiopoietin/Tekinteractions regulate mmp-9
, 百拇医药
expression and retinalneovascularization. Lab Invest 2003;83:1637-1645
11 Weidner N,Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, GaspariniG. Tumor angiogenesis:
a new significant and independentprognostic indicator in early-stage breast carcinoma. J Natl CancerInst
1992;84:1875-1887
12 高国林,杨原, 杨思凤, 任彩文.血管内皮细胞增生是胃癌相关性病变. 世界华人消化杂志 2000;8:282-284
, 百拇医药
13 Gasparini G. Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 2000;5:37-44
14 吴静, 樊代明. 肿瘤血管生成与肿瘤血管抑制治疗. 世界华人消化杂志 2001;9:316-321
15 陶厚权,邹寿椿, 王瑞年, 林言箴.血管生成与胃癌发生之间关系的实验研究.世界华人消化杂志
2003;11:43-46
16 Chen L, Yang Z, Wang G, Wang C. Expression of angiopoietin-2 gene and its receptor Tie2 in hepatocellular carcinoma.
, http://www.100md.com
J Tongji Med Univ 2001;21:228-230
17 Currie MJ, Gunningham SP, Turner K, Han C, Scott PA, Robinson BA, Chong W, Harris AL, Fox SB. Expression of
the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas;regulation by the von Hippel-Lindau
gene and hypoxia. J Pathol 2002;198:502-510
18 Gale NW, Thurston G, Davis S, Wiegand SJ, Holash J, Rudge JS, Yancopoulos GD. Complementary and coordinated
, 百拇医药
roles of the VEGFs and angiopoietins during normal and pathologic vascular formation. Cold Spring Harb Symp
Quant Biol 2002;67:267-273
19 Xing L, Zhang Z, Xu Y. Expression of angiopoietin-2 gene in non-small cell lung cancer. J Huazhong Univ Sci
Technolog Med Sci 2003;23:362-364
20 Caine GJ, Blann AD, Stonelake PS, Stonelake PS, Ryan P, Lip GY. Plasma angiopoietin-1, angiopoietin-2 and Tie-2
, 百拇医药
in breast andprostate cancer:a comparison with VEGF and Flt-1. Eur J Clin Invest 2003;33:883-890
21 李楠,徐采朴, 宋波, 房殿春,杨仕明, 门荣莆.人胃癌组织中金属蛋白酶类基因的过度表达.
华人消化杂志 1998;6:118-120
22 洪照友,俞金龙, 张云生, 高毅.基质金属蛋白酶-9, CD34的表达与肝癌侵袭转移的关系.
世界华人消化杂志 2001;9:170-174
23 Kabashima A, Yao T, Sugimachi K, Tsuneyoshi M. Relationship between biologic behavior and phenotypic expression
, 百拇医药
in intramucosal gastric carcinomas. Hum Pathol 2002;33:80-86
24 Wroblewski LE, Pritchard DM, Carter S, Varro A. Gastrin-stimulated gastric epithelial cell invasion:the role and
mechanism of increased matrix metalloproteinase 9 expression. Biochem J 2002;365:873-879
25 Caudroy S, Polette M, Nawrocki-Raby B, Cao J, Toole BP, Zucker S, Birembaut P. EMMPRIN-mediated MMP regulation
, 百拇医药
in tumor and endothelial cells. Clin Exp Metastasis 2002;19:697-702
26 Shin EY, Ma EK, Kim CK, Kwak SJ, Kim EG. Src/ERK but not phospholipase D is involved in keratinocyte growth
factor-stimulated secretion of matrix metalloprotease-9 and urokinase-type plasminogen activator in SNU-16
human stomach cancer cell. J Cancer Res Clin Oncol 2002;128:596-602
27 Nyberg P, Moilanen M, Paju A, Sarin A, Stenman UH, Sorsa T, Salo T. MMP-9 activation by tumor trypsin-2 enhances
, http://www.100md.com
in vivo invasion of human tongue carcinoma cells. J Dent Res 2002;81:831-835
28 Albo D, Shinohara T, Tuszynski GP. Up-regulation of matrix metalloproteinase 9 by thrombospondin 1 in gastric cancer.
J Surg Res 2002;108:51-60
29 郑伟达,王小众. 基质金属蛋白酶及其抑制物与实验性肝纤维化.世界华人消化杂志 2004;12:428-431
30 Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in
gastriccarcinoma:possible in vivo regulation via induction of proteases. CancerRes 2001;61:2145-2153
编辑 潘伯荣 审读 张海宁, http://www.100md.com( 钱 颉, 刘南植, 程胜平)
