Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas
Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas
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DOI：
10.1002/path.2069
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发表时间：
2006-12-01
影响因子：
7.3
通讯作者：
Ooi, A.
中科院分区：
文献类型：
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作者：
Dobashi, Y.;Watanabe, H.;Ooi, A.
为了阐明自分泌运动因子 (AMF) 在人类肺癌表型和生物学特征中的参与，我们分析了总共 180 个病例的蛋白质和 mRNA 表达。免疫组织化学显示阳性染色率为 67.2%，其中鳞状细胞癌（SCC；90.8%）的阳性率最高，小细胞癌（SmCC；27.8%）的阳性率最低。在鳞状细胞癌中，染色频率和强度与形态分化程度相关。一般来说，免疫印迹分析中的表达水平与免疫组织化学阳性结果吻合良好。然而，蛋白质和 mRNA 水平之间的一致性较差：在 SmCC 和大细胞癌 (LCC) 中，mRNA 表达较高，但蛋白质表达较低。在非小细胞肺癌 (NSCLC) 中，AMF 蛋白水平与肿瘤大小呈负相关，但出现淋巴结转移的肿瘤则表现出较高的 mRNA 表达。在包含所有组织学亚型的培养肺癌细胞中，在所有 10 个细胞系的裂解物中均检测到 AMF。在 6 个细胞系的条件培养基中检测到分泌的 ANIF 蛋白，其中大多数是 SmCC 或 LCC。因此，肺癌的一个特定亚群会分泌 AMF，它可能通过其同源受体进行自分泌刺激来促进细胞运动，并导致 SmCC 和 LCC 中出现的生物侵袭性。此外，蛋白酶体抑制剂的治疗导致五种细胞系中细胞 ANIF 增加，表明细胞内 ANIF 水平受到分泌和蛋白酶体依赖性降解的调节。总之，ANIF 在大部分肺癌中被检测到，并且可能不仅在肿瘤的增殖和/或进展中发挥作用，而且还可能在 SCC 的分化中发挥作用。此外，较高的mRNA表达可能与NSCLC的高转移潜力和蛋白质分泌增加有关，导致更具侵袭性的表型，例如SmCC和LCC的侵袭性。版权所有 (c) 2006 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
To clarify the involvement of autocrine motility factor (AMF) in the phenotype and biological profiles of human lung carcinomas, we analysed protein and mRNA expression in a total of 180 cases. Immunohistochemistry revealed positive staining in 67.2%, with the highest frequency in squamous cell carcinoma (SCC; 90.8%) and the lowest in small cell carcinoma (SmCC; 27.8%). In SCC, the staining frequency and intensity correlated with the degree of morphological differentiation. Generally, the expression levels in immunoblotting analysis corresponded well with immunohistochemical positivity. However, there was less agreement between protein and mRNA levels: in SmCC and large cell carcinomas (LCCs), mRNA showed higher, but protein showed lower expression. Among non-small cell lung carcinomas (NSCLCs), AMF protein levels correlated inversely with tumour size, but tumours exhibiting lymph node metastasis showed higher mRNA expression. In cultured lung carcinoma cells which comprised all histological subtypes, AMF was detected in the lysates of all ten cell lines. Secreted ANIF protein was detected in the conditioned media from six cell lines, most of which were SmCC or LCC. Thus, a particular subset of lung carcinomas secrete AMF, which may promote cell motility via autocrine stimulation through its cognate receptor and cause the biological aggressiveness seen in SmCC and LCC. Moreover, treatment by proteasome inhibitors resulted in increased cellular ANIF in five cell lines, suggesting that intracellular ANIF levels are regulated by both secretion and proteasome-dependent degradation. In conclusion, ANIF was detected in a major proportion of lung carcinomas, and may play a part not only in proliferation and/or progression of the tumours, but also, possibly, in the differentiation of SCC. Furthermore, higher mRNA expression may be related to the high metastatic potential of NSCLC and increased protein secretion, leading to a more aggressive phenotype, such as the invasiveness of SmCC and LCC. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.