An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ.
An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ.
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Syndecan-1（CD138），E-钙粘蛋白和C-MET的表达特征与现场导管乳腺癌中的血管生成和淋巴管生成因子有关。
DOI：
10.1186/bcr1641
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发表时间：
2007
影响因子：
7.4
通讯作者：
Wuelfing, Pia
中科院分区：
文献类型：
--
作者：
Goette, Martin;Kersting, Christian;Radke, Isabel;Kiesel, Ludwig;Wuelfing, Pia
硫酸乙酰肝素蛋白多糖Syndecan-1调节细胞的增殖、黏附、迁移和血管生成。它是肝细胞生长因子受体c-met的辅助受体，其与E-钙粘附素的共表达在上皮-间充质转化过程中受到同步调节。在乳腺癌中，Syndecan-1、E-cadherin和c-met的表达变化与预后不良相关。在这项研究中，我们评估了这些功能相关的预后标志物的共同表达是否构成了乳腺导管原位癌(DCIS)中可能促进细胞增殖和(淋巴)血管生成的表达特征。应用组织芯片免疫组织化学方法检测200例DCIS患者肿瘤组织中Syndecan-1、E-cadherin和c-met的表达。结果与血管生成和淋巴管生成标记物的表达模式相关。用共聚焦免疫荧光显微镜和RT-PCR检测三种预后标记物在人乳腺癌细胞中的共表达。在MCF-7细胞中证实了这三种标志物的共表达和膜共定位。在更具侵袭性的细胞系中，E-钙粘附素的表达逐渐减少，而c-met的表达逐渐增加。组织芯片分析显示，72%的DCIS肿瘤细胞Syndecan-1、67.8%的E-cadherin和48.6%的c-met呈强阳性染色。E-钙粘蛋白的表达与c-met和syndecan-1显著相关。C-met和syndecan-1在单纯DCIS患者亚组中的表达明显高于DCIS合并浸润性癌患者亚组。C-met和syndecan-1的表达水平与HER2的表达水平相关。C-met的表达与内皮素A、B受体、血管内皮生长因子-A和成纤维细胞生长因子受体-1的表达显著相关，而E-钙粘附素的表达与内皮素A受体、血管内皮生长因子-A和血管内皮生长因子-C的表达显著相关。Syndecan-1、E-cadherin和c-Met是DCIS中与血管生成和淋巴管生成因子相关的标志物。这种共表达可能反映了不同信号转导途径的平行激活状态，促进了肿瘤细胞的增殖和血管生成。我们的发现对未来的治疗方法有一定的启示，即多靶点方法，这可能在乳腺癌进展的早期有用。
Heparan sulphate proteoglycan syndecan-1 modulates cell proliferation, adhesion, migration and angiogenesis. It is a coreceptor for the hepatocyte growth factor receptor c-met, and its coexpression with E-cadherin is synchronously regulated during epithelial-mesenchymal transition. In breast cancer, changes in the expression of syndecan-1, E-cadherin and c-met correlate with poor prognosis. In this study we evaluated whether coexpression of these functionally linked prognostic markers constitutes an expression signature in ductal carcinoma in situ (DCIS) of the breast that may promote cell proliferation and (lymph)angiogenesis. Expression of syndecan-1, E-cadherin and c-met was detected immunohistochemically using a tissue microarray in tumour specimens from 200 DCIS patients. Results were correlated with the expression patterns of angiogenic and lymphangiogenic markers. Coexpression of the three prognostic markers was evaluated in human breast cancer cells by confocal immunofluorescence microscopy and RT-PCR. Coexpression and membrane colocalization of the three markers was confirmed in MCF-7 cells. E-cadherin expression decreased, and c-met expression increased progressively in more aggressive cell lines. Tissue microarray analysis revealed strong positive staining of tumour cells for syndecan-1 in 72%, E-cadherin in 67.8% and c-met in 48.6% of DCIS. E-cadherin expression was significantly associated with c-met and syndecan-1. Expression of c-met and syndecan-1 was significantly more frequent in the subgroup of patients with pure DCIS than in those with DCIS and a coexisting invasive carcinoma. Levels of c-met and syndecan-1 expression were associated with HER2 expression. Expression of c-met significantly correlated with expression of endothelin A and B receptors, vascular endothelial growth factor (VEGF)-A and fibroblast growth factor receptor-1, whereas E-cadherin expression correlated significantly with endothelin A receptor, VEGF-A and VEGF-C staining. Syndecan-1, E-cadherin and c-met constitute a marker signature associated with angiogenic and lymphangiogenic factors in DCIS. This coexpression may reflect a state of parallel activation of different signal transduction pathways, promoting tumour cell proliferation and angiogenesis. Our findings have implications for future therapeutic approaches in terms of a multiple target approach, which may be useful early in breast cancer progression.
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影响因子：
4.8
作者：
Elenius, V;Götte, M;Bernfield, M
通讯作者：
Bernfield, M
DOI：
10.1152/ajpheart.2000.279.6.h2865
发表时间：
2000-12-01
影响因子：
4.8
作者：
Haug, C;Schmid-Kotsas, A;Rozdzinski, E
通讯作者：
Rozdzinski, E
DOI：
10.1083/jcb.200404171
发表时间：
2004-10-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Beauvais DM;Burbach BJ;Rapraeger AC
通讯作者：
Rapraeger AC
影响因子：
6.2
作者：
Barbareschi, M;Maisonneuve, P;Doglioni, C
通讯作者：
Doglioni, C
影响因子：
11.2
作者：
Bertotti, A;Comoglio, PM;Trusolino, L
通讯作者：
Trusolino, L