Expression of MUC-1 epitopes on normal bone marrow:: Implications for the detection of micrometastatic tumor cells
Expression of MUC-1 epitopes on normal bone marrow:: Implications for the detection of micrometastatic tumor cells
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DOI：
10.1200/jco.1999.17.5.1535
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发表时间：
1999-05-01
影响因子：
45.3
通讯作者：
Kanz, L
中科院分区：
文献类型：
--
作者：
Brugger, W;Bühring, HJ;Kanz, L
目的：癌症相关粘蛋白MUC-1的表达被认为仅限于上皮细胞，并用于实体瘤患者（包括乳腺癌患者）的微转移肿瘤细胞检测。材料和方法：采用不同的抗MUC-1特异性单克隆抗体，通过流式细胞术和免疫细胞学分析来自健康志愿者的骨髓（BM）单核细胞和纯化的CD 34（+）细胞上的MUC-1表达。结果：令人惊讶的是，2%至10%的正常人骨髓单个核细胞表达MUC-1，如由抗MUC-1抗体BM-2（2 E11）、BM-7、12 H12、MAM-6和HMFG-1所定义的，相反，未检测到识别MUC-1的BM-8和HMFG-2表位的两种抗体。来自正常BM的MUC-1（+）细胞主要由成红细胞和正常成红细胞组成。与此一致，在体外培养以分化成红系的正常CD 34（+）细胞在第7天的原成红细胞中显示出强烈的MUC-1表达。这些细胞的蛋白质印迹证实了反应物质是已知的高分子量MUC-1蛋白。我们的数据表明，一些MUC-1表位在正常BM细胞上，特别是在红系细胞上表达。因此，应用抗MUC-1抗体检测BM或外周血祖细胞中的播散性肿瘤细胞可能提供假阳性结果，并且仅可以选择仔细评估的抗MUC-1抗体（例如，HMFG-2）。此外，癌症患者中的MUC-1靶向免疫治疗可能会受到红细胞生成抑制的阻碍。J Clin Oncol 17：1535-1544. (C)1999年，美国临床肿瘤学会。
Purpose: The expression of the carcinoma-associated mucin MUC-1 is thought to be restricted to epithelial cells and is used for micrometastatic tumor cell detection in patients with solid tumors, including those with breast cancer. Little is known, however, about the expression of MUC-1 epitopes in normal hematopoietic cells.Materials and Methods: MUC-1 expression was analyzed by flow cytometry and immunocytology on bone marrow (BM) mononuclear cells and purified CD34(+) cells from healthy volunteers, using different anti-MUC-1-specific monoclonal antibodies. In addition, Western blotting of MUC-1 proteins was performed.Results: Surprisingly, 2% to 10% of normal human BM mononuclear cells expressed MUC-1, as defined by the anti-MUC-1 antibodies BM-2 (2E11), BM-7, 12H12, MAM-6, and HMFG-1, In contrast, two antibodies recognizing the BM-8 and the HMFG-2 epitopes of MUC-1 were not detected. MUC-1(+) cells from normal BM consisted primarily of erythroblasts and normoblasts. In agreement with this, normal CD34(+) cells cultured in vitro to differentiate into the erythroid lineage showed a strong MUC-1 expression on day 7 proerythroblasts. Western blotting of these cells confirmed that the reactive species is the known high molecular weight MUC-1 protein.Conclusion: Our data demonstrate that some MUC-1 epitopes are expressed on normal BM cells and particularly on cells of the erythroid lineage, Hence the application of anti-MUC-1 antibodies for disseminated tumor cell detection in BM or peripheral blood progenitor cells may provide false-positive results, and only carefully evaluated anti-MUC-1 antibodies (eg, HMFG-2) might be selected. Furthermore, MUC-1-targeted immunotherapy in cancer patients might be hampered by the suppression of erythropoiesis. J Clin Oncol 17:1535-1544. (C) 1999 by American Society of Clinical Oncology.