Hanaoka J, Kontani K, Sawai S, Ichinose M, Tezuka N, Inoue S, Fujino S, Ohkubo I
Second Department of Surgery, Shiga University of Medical Science, Seta, Otsu, Japan.
Cancer. 2001 Oct 15;92(8):2148-57. doi: 10.1002/1097-0142(20011015)92:8<2148::aid-cncr1557>3.0.co;2-6.
MUC4 has been cloned from tracheobronchial mucosa cDNA and reportedly is highly expressed in some human malignancies, including lung carcinoma. However, little is known about molecular and biologic characteristics. The authors analyzed expression levels of MUC4 mRNA and protein in lung carcinoma cells and analyzed the immunogenicity of this mucin.
Nine cultured lung carcinoma cell lines and 29 tumor samples from patients with lung carcinoma were examined by Northern hybridization for MUC4 mRNA expression and by flow cytometry or an immunohistochemical staining for its protein expression. Sera from the patients were examined for their reactivity with MUC4 by enzyme-linked immunosorbent assay.
Forty-four percent of the cell lines and 72% of the tumor samples showed high levels of MUC4 mRNA expression. Although MUC4 protein was not detected in any live carcinoma cell lines by flow cytometry using rabbit antisera reactive with the MUC4 core, pretreatment with paraformaldehyde and sialidase resulted in successful detection of the protein in 50% of the cell lines. An immunohistochemical study revealed that 67% of the tumors exhibited MUC4 protein expression without any digestion. In 29% of the patients, high levels of anti-MUC4 immunoglobulin M or immunoglobulin G were detected.
MUC4 protein expression was elevated in lung carcinoma tissues because of the increase in its mRNA expression and deglycosylation on its core. This mucin is sufficiently immunogenic to elicit humoral and cellular immunity specific for MUC4 in patients with malignant disease. MUC4 is expected to be useful as a target antigen in immunotherapy for patients with carcinoma of the lung.
MUC4已从气管支气管黏膜cDNA中克隆出来，据报道在包括肺癌在内的一些人类恶性肿瘤中高度表达。然而，对其分子和生物学特性知之甚少。作者分析了肺癌细胞中MUC4 mRNA和蛋白的表达水平，并分析了这种黏蛋白的免疫原性。
通过Northern杂交检测9种培养的肺癌细胞系和29例肺癌患者的肿瘤样本中MUC4 mRNA的表达，通过流式细胞术或免疫组织化学染色检测其蛋白表达。采用酶联免疫吸附试验检测患者血清与MUC4的反应性。
44%的细胞系和72%的肿瘤样本显示MUC4 mRNA高水平表达。虽然使用与MUC4核心反应的兔抗血清通过流式细胞术在任何活的癌细胞系中均未检测到MUC4蛋白，但用多聚甲醛和唾液酸酶预处理后，50%的细胞系成功检测到该蛋白。免疫组织化学研究显示，67%的肿瘤在未进行任何消化的情况下呈现MUC4蛋白表达。在29%的患者中检测到高水平的抗MUC4免疫球蛋白M或免疫球蛋白G。
由于MUC4 mRNA表达增加及其核心糖基化缺失，肺癌组织中MUC4蛋白表达升高。这种黏蛋白具有足够的免疫原性，可在恶性疾病患者中引发针对MUC4的体液免疫和细胞免疫。MUC4有望作为肺癌患者免疫治疗的靶抗原。
