肝素酶和碱性成纤维细胞生长因子与胃癌转移和预后的关系
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摘要
目的探讨肝素酶(heParanase)和碱性成纤维细胞生长因子(bFGF)在胃癌组织中表达及其与临床特征之间的关系。
方法采用免疫组织化学方法检测80例胃癌石蜡切片和20例正常胃黏膜中肝素酶和bFGF的表达情况;分析两者分别表达及共表达与胃癌患者年龄、性别、分期,分化程度,浸润深度、淋巴结转移的关系。
结果免疫组织化学染色结果表明:80例胃癌中有49例(61.3%)呈肝素酶阳性表达,52例(65.0%)呈bFGF阳性表达,主要表达在癌细胞质和(或)细胞膜中,在正常胃黏膜上皮则呈阴性表达,肝素酶和bFGF在胃癌中表达明显增高(P＜0.05),且两者的表达具有明显的相关性(P＜0.05)。两者单独表达和共表达均与胃癌的分化程度、分期、浸润深度、淋巴结转移有关,与患者年龄、性别无关。
结论肝素酶和bFGF蛋白在胃癌组织中的表达较正常胃黏膜上皮明显上调,两者单独表达和共表达与胃癌的侵袭及转移能力密切相关。
Objective
To assess protein expression levels of heparanase and basic fibroblast growth factor(bFGF) and the relation between their expressionand biological factors in human gastric carcinoma.
Methods
A total of 80 paraffin-embedded gastric cancer and 20 normal specimens were studied by immunohistochemisty to evaluate the protein expression status of heparanase and bFGF. The relation was analyzed among the protein expression and age, sex, TNM stage, cell differentiation, invasion depth, lymphatic metastasis .
Results
Immunohistochemistry showed that 49 specimens were heparanase positive and 52 ones were bFGF positive among 80 cancer specimens. Both human heparanase and bFGF were highly expressed in cancer cell in contrast to none expression in normal tissue . Expression was in both cytoplasm and membranous. The agreement between heparanase and bFGF expression was significant. A significant correlation was found between the expression of either protein and cell differentiation ,TNM stage, invasion deapth, lymphatic metastasis.
Conclusion
Both heparanase and bFGF were highly expressed in colorectal cancer .They may play important roles in tumor invasion, metastasis and angiogenesis.
方法采用免疫组织化学方法检测80例胃癌石蜡切片和20例正常胃黏膜中肝素酶和bFGF的表达情况;分析两者分别表达及共表达与胃癌患者年龄、性别、分期,分化程度,浸润深度、淋巴结转移的关系。
结果免疫组织化学染色结果表明:80例胃癌中有49例(61.3%)呈肝素酶阳性表达,52例(65.0%)呈bFGF阳性表达,主要表达在癌细胞质和(或)细胞膜中,在正常胃黏膜上皮则呈阴性表达,肝素酶和bFGF在胃癌中表达明显增高(P＜0.05),且两者的表达具有明显的相关性(P＜0.05)。两者单独表达和共表达均与胃癌的分化程度、分期、浸润深度、淋巴结转移有关,与患者年龄、性别无关。
结论肝素酶和bFGF蛋白在胃癌组织中的表达较正常胃黏膜上皮明显上调,两者单独表达和共表达与胃癌的侵袭及转移能力密切相关。
Objective
To assess protein expression levels of heparanase and basic fibroblast growth factor(bFGF) and the relation between their expressionand biological factors in human gastric carcinoma.
Methods
A total of 80 paraffin-embedded gastric cancer and 20 normal specimens were studied by immunohistochemisty to evaluate the protein expression status of heparanase and bFGF. The relation was analyzed among the protein expression and age, sex, TNM stage, cell differentiation, invasion depth, lymphatic metastasis .
Results
Immunohistochemistry showed that 49 specimens were heparanase positive and 52 ones were bFGF positive among 80 cancer specimens. Both human heparanase and bFGF were highly expressed in cancer cell in contrast to none expression in normal tissue . Expression was in both cytoplasm and membranous. The agreement between heparanase and bFGF expression was significant. A significant correlation was found between the expression of either protein and cell differentiation ,TNM stage, invasion deapth, lymphatic metastasis.
Conclusion
Both heparanase and bFGF were highly expressed in colorectal cancer .They may play important roles in tumor invasion, metastasis and angiogenesis.
引文
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[38]Riedel F,Gotte K,Schwalb J,et al.Coexpression of VEGF and bFGF is associated with increased vascular density in head and neck carcinomas.Laryngorhinootologie,2000,79(12):730-735.
[39]Cucina A,Borrelli V,Lucarelli M,et al.Autocrine production of basic fibroblast growth factor translated from novel synthesized mRNA mediates thrombin-induced mitogenesis in smooth muscle cells.Cell Biochem Funct,2002,20(1):39-46
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[2]Vaday G,Lider O.Extracellular matrix moieties,cytokines,and enzymes:dynamic effects on immune cell behavior and inflammation.J Leuk Biol,2000,67(2):149-158.
[3]Hulett D,Hornby J,Ohms S,et al.Identification of active-site residues of the prometastasis endoglycosidase hePamnase.Biochemistry,2000,39(51):15659-15667
[4]McKenzie E,Tyson K,Stamp A,et al.Cloning and expression profiling of Hpa2,a novel mammalian heparanase family member.Biochem BioPhys Res Commun,2000,276(3):1170-1177.
[5]Okada M,Thiery J,Jouanneau J.Firoblast growth factor-2.Int J Biochem,2000,32(3):263-267.
[6]Delrieu L.The high molecular weight isoforms of basic fibroblast growth factor (FGF-2):an insight into an intracrine mechanism.FEBS Lett,2000,468(1):6-10.
[7]Dong J,Kukula AK,Toyoshima M,et al.Genomic organization and chromosome localization of the newly identified human heparanase gene.Gene,2000,253(2):171-178.
[8]Parish CR,Freeman C,Hulett MD.Heparanase:a key enzyme involved in cell invasion.Biochim Biophys Acta,2001,1471(3):99-108.
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[10]Schubert SY,Ilan N,Shushy M,et al.Human heparanase nuclear localization and enzymatic activity.Lab Invest,2004,84(5):535-544.
[11]Andela VB,Schwarz EM,Puzas JE,et al.Tumor metastasis and the reciprocal regulation of prometastatic and antimeastatic factors by nuclear factor kappa B.Cancer Res,2000,60(23):6557-6562.
[12]Marchetti D,Reiland J,Erwin B,et al.Inhibition of heparanase activity and heparanase-induced angiogenesis by suramin analogues.Int J Cancer,2003,104(2):167-174.
[13]Sasaki M,Ito T,Kashmi M,et al.Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro.Mediator Inflamm,2001,10(5):259-267
[14]Zcharia E,Zamir E.Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis.Biology Neoplasm,2001,6(2):311-322.
[15]Enod K,Maejara U,Baba H,et al.Heparinase gene expression and metastasis potential in human gastric cancers.Anticancer Res,2001,21(5):3365-3369.
[16]Takaoka M,Naomoto Y,Ohkawa T,et al.Heparinase expression correlates with invasion and poor prognosis in gastic cancers.LabInvest,2003,83(5):613-622.
[17]KolioPanos A,Friess H,Kleeff J,et al.Heparanase expression in primary and metastatic pancreatic cancer.Cancer Res,2001,61(12):4655-4659.
[18]Gohji K,Okamoto M,Kitazawa S,et al.Heparanase protein and gene expression in bladder cancer.J Urol,2001,166(4):1286-1290
[19]Kurokawa H,Katsube K,Podyma KA,et al.Heparinase and tumor invasion patterns in human oral squamous cell carcinoma xenografts.Cancer Sci,2003,94(1):277-285.
[20]Ginath S,Menczer J,Friedmann Y,et al.Expression of heparanase,Mdm2,and erbB2 in ovarian cancer.Int J Oncol,2001,18(6):1133-1144
[21]Edovitsky E,Elkin M,Zcharia E,et al.Heparanase gene silencing,tumor invasiveness,angiogenesis,and metastasis.J Natl Cancer Inst,2004,96(16):1219-1230.
[22]张水军,郭文治,赵永福.乙酰肝素酶2蛋白的表达与胰腺癌浸润、转移的关系及其意义.中国普通外科杂志,2006,15(6):466-468.
[23]EIAssal ON,Yamanoi A,Ono T,et al.The clinicopathological significance of heparinase and basic fibroblast growth factor expression in hepatocellular carcinoma.Clin Cancer Res,2001,7(5):1299-1305.
[24]曹厚军,方勇,张行.乙酰肝素酶在胃癌组织中的表达及临床意义.中华消化杂志,2005,25(3):180-181.
[25]Tang W,Nakamara Y,Tsajimoto M,et al.Heparanase:a key enzyme in invasion and metastasis of gastric carcinoma..Mod Pathol,2002,15(6):593-598.
[26]Vlodavasky I,Atzmon R,Elkin M,et al.Mammalian heparanase,involvement in cancer metastasis,angiogenesis and normal development.Semin Cancer Biol,2002,12(2):121-129
[27]Elkin M,Blackhall FH,Jayson GC,et al.Heparanase as mediator of angiogenesis mode of action.FASEB,2001,15(9):1661-1663.
[28]Marchetti D,Li J,Shen R.Astrocytes contribute to the brain-metastatic specificity of melanoma cells by Producing heparanase.Cancer Res,2000,60(17):4767-4770.
[29]Ornit DM.FGFs,heparin sulfate and FGFRs:complex interactions essential for development.Bioassays,2000,22(2):108-112
[30]Friedegund M,Mark N,Mei H,et al.Human Melanoma Progression in Skin Reconstructs:Biological Significance of bFGF.Am.J Pathol,2000,156(2):193-196
[31]Tang Y,Ma W,Yan R.et al.Modulation of neurod expression and photoreceptor production by bFGF.Invest.Ophthalmol.Vis.Sci,2005;46:2393.
[32]Ishihara M,Fujita M,Obara K,et al.Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair,angiogenesis,and tumor growth.Curr Drug Deliv.2006,3(4):351-358.
[33]林卫,彭芝兰,郑艾,等.碱性成纤维细胞生长因子与卵巢癌的关系.中华医学遗传学杂志,2003,20(6):532-535
[34]赵仲生,茹国庆,马杰.碱性成纤维细胞生长因子mRNA表达与微血管密度和胃癌的发展及预后.中华病理学杂志,2003,32(1):57-58
[35]Bian XW,Du LL,Shi JQ,et al.Correlation of bFGF,FGFR-1 and VEGF expression with vascularity and malignancy of human astrocytomas.Anal Quant Cytol Histol,2000,22(3):267-274.
[36]Akinori I,Motohisa K,Yasuteru Yoshinaga,et al.Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) levels,as prognostic indicators in NSCLC.J.Cardiothorac.Surg.,2004,25(3):443-448.
[37]Boelaert K,McCabe CJ,Tannahill LA,et al.Pituitary tumor transforming gene and fibroblast growth factor-2 expression:potential prognostic indicators in differentiated thyroid cancer.J Clin Endocrinol Metab,2003,88(5):2341-2347.
[38]Riedel F,Gotte K,Schwalb J,et al.Coexpression of VEGF and bFGF is associated with increased vascular density in head and neck carcinomas.Laryngorhinootologie,2000,79(12):730-735.
[39]Cucina A,Borrelli V,Lucarelli M,et al.Autocrine production of basic fibroblast growth factor translated from novel synthesized mRNA mediates thrombin-induced mitogenesis in smooth muscle cells.Cell Biochem Funct,2002,20(1):39-46
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