Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients.

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients.
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DOI:
10.1038/sj.bjc.6604621
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发表时间:
2008-09-16
影响因子:
8.8
通讯作者:
Atanackovic, D.
Atanackovic, D.
中科院分区:
医学1区
文献类型:
--
作者:
Panse, J.;Friedrichs, K.;Marx, A.;Hildebrandt, Y.;Luetkens, T.;Bartels, K.;Horn, C.;Stahl, T.;Cao, Y.;Milde-Langosch, K.;Niendorf, A.;Kroeger, N.;Wenzel, S.;Leuwer, R.;Bokemeyer, C.;Hegewisch-Becker, S.;Atanackovic, D.

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趋化因子在协调细胞迁移中的能力被包括恶性肿瘤在内的不同(病理)生物网络所利用。然而,除了CXCR 4/CXCL 12外,关于肿瘤相关趋化因子表达与实体瘤(如乳腺癌)的发展和进展之间的关系知之甚少。在这项研究中,微阵列分析揭示了乳腺癌标本中趋化因子CXCL 13的过度表达。这一发现证实了实时聚合酶链反应在一个更大的样本集(n=34)和细胞系,并验证蛋白质水平进行蛋白质印迹,ELISA和免疫组化。CXCL 13的受体CXCR 5在恶性和健康乳腺组织中的水平较低,并且在体外未检测到表面表达。然而,我们观察到乳腺癌组织中CXCL 13和CXCR 5的表达之间存在强相关性(P=0.0004),表明CXCR 5在体内具有生物学相关作用。最后,我们检测到与对照组(n=44)和无疾病患者(n=48)相比,转移性疾病患者(n=54)中CXCL 13的血清浓度显著升高。总之,CXCL 13在乳腺癌组织中过表达,并且在患有转移性疾病的乳腺癌患者中可以发现该细胞因子的血清水平升高,表明CXCL 13在乳腺癌进展中发挥作用,这表明CXCL 13可能作为有用的治疗靶点和/或诊断标记物在这种恶性肿瘤中。
The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n=34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P=0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n=54) as compared with controls (n=44) and disease-free patients (n=48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy.
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