CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival
CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival
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DOI：
10.1016/j.ejca.2009.06.026
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发表时间：
2009-09-01
影响因子：
8.4
通讯作者：
Pfeffer, Ulrich
中科院分区：
文献类型：
--
作者：
Mirisola, Valentina;Zuccarino, Ambra;Pfeffer, Ulrich
细胞因子 C-X-C 基序趋化因子 12 (CXCL12) 由转移靶组织合成，已被证明可以吸引表达受体 C-X-C 趋化因子受体 4 型 (CXCR4) 的肿瘤细胞。然而，最近报道CXCL12的表观遗传沉默会增加乳腺癌细胞的转移潜力，并且将细胞因子基因重新引入MDA-MB-231乳腺癌细胞会减少体内形成的转移数量。因此，我们希望了解 CXCL12 表达是否与人类乳腺癌患者的无复发生存率和总生存率相关。通过免疫组织化学分析了 100 个存档乳腺癌样本和 408 例乳腺癌微阵列数据集中的 C-X-C 基序趋化因子 12 (CXCL12) 和 C-X-C 趋化因子受体 4 (CXCR4) 的表达。通过单变量和多变量COX回归分析对数据进行分析。CXCL12和CXCR4由上皮肿瘤细胞以及基质细胞和内皮细胞表达。微阵列基因表达分析和免疫组织化学显示，CXCL12 的表达而非 CXCR4 的表达与雌激素受体阳性和阴性癌症的无病生存和总生存显着相关。雌激素受体α的表达与CXCL12的表达不相关。CXCL12是一个强有力的、独立的预后标志物。我们提出，通过自分泌 CXCL12 产生而使受体饱和，会减少对释放 CXCL12 的转移靶组织的趋化性。 (C) 2009 Elsevier Ltd. 保留所有权利。
The cytokine C-X-C motif chemokine 12 (CXCL12) is synthesised by metastasis target tissues and has been shown to attract tumour cells that express the receptor, C-X-C chemokine receptor type 4 (CXCR4). However, epigenetic silencing of CXCL12 has recently been reported to increase the metastatic potential of breast cancer cells and the reintroduction of the cytokine gene into MDA-MB-231 breast carcinoma cells decreases the number of metastases formed in vivo. We therefore wished to know whether CXCL12 expression correlates with relapse-free and overall survival in human breast cancer patients.The expression of C-X-C motif chemokine 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4) was analysed in 100 archival breast cancer samples by immunohistochemistry and in two breast cancer microarray datasets of 408 cases. Data were analysed by univariate and multivariate COX regression analyses.CXCL12 and CXCR4 are expressed by epithelial tumour cells and by stromal and endothelial cells. Microarray gene expression analysis and immunohistochemistry revealed that expression of CXCL12 but not of CXCR4 significantly correlates with disease-free and overall survival in oestrogen receptor-positive and -negative cancers. The expression of the oestrogen receptor a and that of CXCL12 do not correlate.CXCL12 is a strong, independent prognostic marker. We propose that saturation of the receptor through autocrine CXCL12 production reduces chemotaxis towards CXCL12-releasing metastasis target tissues. (C) 2009 Elsevier Ltd. All rights reserved.