Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow
Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow
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DOI：
10.1007/s10585-005-3222-y
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发表时间：
2005-01-01
影响因子：
4
通讯作者：
Price, JE
中科院分区：
文献类型：
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作者：
Cabioglu, N;Sahin, A;Price, JE
乳腺癌细胞中CXCR4趋化因子受体与配体CXCL12/SDF-1 α之间的相互作用被认为在乳腺癌转移中起重要作用。在这项初步研究中，我们在可手术乳腺癌患者的原发肿瘤样本中测量了CXCR4的表达以及其他生物标志物（包括HER2-neu和EGFR）的表达，以测试这些生物标志物单独或联合使用是否可以提示乳腺癌转移到骨髓的可能性很高。骨髓细胞角蛋白（CK）阳性细胞经CK 7/8抗体偶联磁珠富集后流式细胞术鉴定。采用间接亲和素-生物素辣根过氧化物酶法对原发肿瘤（n = 18）进行CXCR4、HER2-neu、EGFR和PCNA特异性抗体染色。大多数患者有T2/T3肿瘤（72%），或淋巴结受累（67%）作为病理特征，更能指示高风险乳腺癌。18例患者中有7例（39%）发现CXCR4细胞质高表达，而18例患者中有6例（33%）发现骨髓CK阳性。每5 × 10(4)个富集的BM细胞中CK+细胞数为236（范围，20-847）个。在原发性肿瘤中，骨髓中CK+细胞的存在与CXCR4单独表达或EGFR和/或HER2-neu表达增加相关（P = 0.013, P = 0.005和P = 0.025）。此外，3例高CK阳性患者（每5 × 10(4)个富集的骨髓细胞中有bbb236个CK+）在骨髓中只表达高水平的CXCR4与EGFR/HER2-neu （P = 0.001）。我们的数据表明，CXCR4在乳腺癌中的高表达可能是预测骨髓分离肿瘤细胞的潜在标志物。CXCR4与EGFR/HER2-neu的共表达可能进一步预测骨髓中高CK阳性患者的特定亚群。
Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1 alpha are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin-biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK+ cells was 236 (range, 20-847) per 5 x 10(4) enriched BM cells. The presence of CK+ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (> 236 CK+ per 5 x 10(4) enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.