Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor-Negative Tumors
Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor-Negative Tumors
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DOI：
10.1155/2011/723650
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Sang, Qing-Xiang Amy
中科院分区：
文献类型：
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作者：
Khamis, Zahraa I.;Sahab, Ziad J.;Sang, Qing-Xiang Amy
研究工作集中在上皮癌细胞的遗传改变上。上皮-间质相互作用在癌症的发生、发展、侵袭、血管生成和转移中起着至关重要的作用;然而，间质在人类乳腺肿瘤发生中与上皮细胞的雌激素受体（ER）状态相关的积极作用尚未探讨。利用蛋白质组学和生物化学方法，我们在ER阳性和ER阴性人类乳腺癌组织中鉴定了两种可能影响乳腺癌恶变的基质蛋白。在ER阳性组织的白细胞和ER阴性组织的内皮细胞中分别检测到两种假定的生物标志物，T细胞受体α（TCR-α）和锌指和具有KRAB结构域的BRCA 1相互作用蛋白（ZBRK 1）。我们的数据表明白细胞在浸润性乳腺肿瘤中的免疫抑制作用，提出ZBRK 1在雌激素受体调节和血管生成中的多功能性质，并证明ER阴性人乳腺癌的侵袭性。该研究项目可能会为乳腺癌患者的治疗确定新的基质药物靶点。
Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-alpha) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.