Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma.
Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma.
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DOI：
10.1111/j.1349-7006.2009.01244.x
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发表时间：
2009-09
期刊：
影响因子：
5.7
通讯作者：
Weil RJ
中科院分区：
文献类型：
--
作者：
Alper O;Stetler-Stevenson WG;Harris LN;Leitner WW;Ozdemirli M;Hartmann D;Raffeld M;Abu-Asab M;Byers S;Zhuang Z;Oldfield EH;Tong Y;Bergmann-Leitner E;Criss WE;Nagasaki K;Mok SC;Cramer DW;Karaveli FS;Goldbach-Mansky R;Leo P;Stromberg K;Weil RJ
血液循环中肿瘤来源蛋白的鉴定可能有助于癌症的早期检测和治疗反应的评估。为了鉴定循环肿瘤来源的蛋白，用人乳腺癌细胞调节的浓缩培养基免疫小鼠。从正常上皮细胞和肿瘤细胞的条件培养基中筛选杂交瘤产生的抗体。进一步表征了抗体与肿瘤细胞条件培养基的选择性反应。这导致了一种单克隆抗体（Alper-p280）的开发，该抗体可与新鉴定的280 kda分泌的人丝蛋白a变体反应。在ELISA试验中使用Alper-p280检测患者血浆样品中的循环丝蛋白a。对134名脑癌、乳腺癌或卵巢癌患者、15名活动性关节炎患者和76名健康对照者的血浆样本进行了分析。采用western blotting、免疫组织化学、电子显微镜和共聚焦显微镜分析人细胞系和组织中丝蛋白a的水平。143例乳腺癌和原发性脑肿瘤患者中，109例患者血浆中检测到循环丝蛋白a。血浆丝蛋白a水平对胶质母细胞瘤的敏感性为89.5%(95%可信区间[CI] = 0.67% ~ 0.99%)，特异性为97.8% (95% CI = 0.88% ~ 0.99%)，临界值为21.0 ng/mL。血浆丝蛋白a水平（bb0 36.0 ng/mL）对转移性乳腺癌的敏感性为96.7% (95% CI = 0.80% ~ 0.99%)，特异性为67.8% （95% CI = 0.54% ~ 0.79%）。丝蛋白a水平在恶性乳腺或脑组织中升高，而在正常对照组织中没有升高。丝蛋白a定位于MDA.MB的溶酶体。231个乳腺癌细胞，但在正常的人类乳腺上皮细胞中没有，这表明丝蛋白a可能经历了癌症特异性的加工。血浆丝蛋白a似乎是高度星形细胞瘤或转移性乳腺癌患者特异性和敏感的标志物。与Alper-p280一起，其他新的癌症生物标志物已被确定并正在开发中，用于乳腺癌和高级星形细胞瘤的诊断，以及用于治疗反应的评估。
Identification of tumor-derived proteins in the circulation may allow for early detection of cancer and evaluation of therapeutic responses. To identify circulating tumor-derived proteins, mice were immunized with concentrated culture medium conditioned by human breast cancer cells. Antibodies generated by hybridomas were screened against conditioned media from both normal epithelial cells and tumor cells. Antibody selectively reacting with tumor cell-conditioned media was further characterized. This led to the development of a monoclonal antibody (Alper-p280) that reacts with a newly identified 280-kDa secreted variant of human filamin-A. Circulating filamin-A was detected in patient plasma samples using Alper-p280 in an ELISA assay. Human plasma samples from 134 patients with brain, breast, or ovarian cancer, 15 patients with active arthritis, and 76 healthy controls were analyzed. Filamin-A protein levels in human cell lines and tissues were analyzed by western blotting, immunohistochemistry, and electron and confocal microscopy. Circulating filamin-A was detected in the plasma of 109 of 143 patients with breast cancer and primary brain tumors. Plasma levels of filamin-A showed 89.5% sensitivity (95% confidence interval [CI] = 0.67% to 0.99%) and 97.8% specificity (95% CI = 0.88% to 0.99%) for glioblastoma at a cut-off of 21.0 ng/mL. Plasma levels of filamin-A (>36.0 ng/mL) had 96.7% sensitivity (95% CI = 0.80% to 0.99%) and 67.8% specificity (95% CI = 0.54% to 0.79%) for metastatic breast cancer. Filamin-A levels were increased in malignant breast or brain tissues, but not in normal control tissues. Filamin-A localized to lysosomes in MDA.MB.231 breast cancer cells, but not in normal human mammary epithelial cells, suggesting that filamin-A may undergo cancer-specific processing. Plasma filamin-A appears to be a specific and sensitive marker for patients with high-grade astrocytoma or metastatic breast cancer. Additional novel cancer biomarkers have been identified and are being developed alongside Alper-p280 for use in diagnosis of breast carcinoma and high-grade astrocytoma, and for use in the evaluation of therapeutic responses.
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影响因子：
4.8
作者：
Marti, A;Luo, ZJ;Avruch, J
通讯作者：
Avruch, J
影响因子：
4.8
作者：
Sasaki, A;Masuda, Y;Watanabe, K
通讯作者：
Watanabe, K
影响因子：
45.3
作者：
Iwanicki-Caron, Isabelle;Di Fiore, Frederic;Michel, Pierre
通讯作者：
Michel, Pierre
影响因子：
4.4
作者：
Keshamouni, VG;Michailidis, G;Omenn, GS
通讯作者：
Omenn, GS
影响因子：
6.4
作者：
Lin, Jian-Feng;Xu, Jun;Zhao, Fu-Kun
通讯作者：
Zhao, Fu-Kun