RRC ID 42782
著者 Dobashi Y, Watanabe H, Sato Y, Hirashima S, Yanagawa T, Matsubara H, Ooi A.
タイトル Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas.
ジャーナル J Pathol
Abstract 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 AMF 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 AMF in five cell lines, suggesting that intracellular AMF levels are regulated by both secretion and proteasome-dependent degradation. In conclusion, AMF 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.
巻・号 210(4)
ページ 431-40
公開日 2006-12-1
DOI 10.1002/path.2069
PMID 17029220
MeSH Adenocarcinoma / chemistry Adenocarcinoma / pathology Carcinoma, Large Cell / chemistry Carcinoma, Large Cell / pathology Carcinoma, Non-Small-Cell Lung / chemistry Carcinoma, Non-Small-Cell Lung / pathology Carcinoma, Small Cell / chemistry Carcinoma, Small Cell / pathology Carcinoma, Squamous Cell / chemistry Carcinoma, Squamous Cell / pathology Cell Differentiation Cell Line, Tumor Cysteine Proteinase Inhibitors / pharmacology Female Glucose-6-Phosphate Isomerase / analysis* Humans Immunohistochemistry / methods In Situ Hybridization / methods Lung Neoplasms / chemistry* Lung Neoplasms / pathology Lymphatic Metastasis / pathology Male Neoplasm Proteins / analysis RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured
IF 6.021
引用数 11
WOS 分野 PATHOLOGY ONCOLOGY
リソース情報
ヒト・動物細胞