Midulla M, Verma R, Pignatelli M, Ritter M A, Courtenay-Luck N S, George A J
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Cancer Res. 2000 Jan 1;60(1):164-9.
ED-B fibronectin (FN) is a FN isoform derived from alternative splicing of the primary transcript of a single gene. Its expression on tumor stroma and neoformed tumor vasculature and its absence, with few exceptions, in normal adult tissues imply a prognostic and diagnostic value for ED-B FN. We investigated the location and source of ED-B FN because this will be of importance both in understanding its role in tumor development and in designing strategies to target this molecule. We have confirmed that ED-B FN is expressed in the majority of breast and colorectal carcinoma tissue samples, with strong immunohistochemical staining around the tumor cells and in the tumor stroma. No staining of tumor neovasculature was seen. ED-B FN is produced by a range of tumor and endothelial (both primary and transformed) cell lines, as detected by reverse transcription-PCR, but is not expressed at the plasma membrane. Strong expression of human ED-B FN is seen in tumor xenografts. These data indicate that neoplastic cells can act as the source of ED-B FN in tumors. The lack of cell surface expression on tumor cell lines has clear implications for the design of therapeutic strategies which target this molecule.
ED-B 纤连蛋白（FN）是一种通过单个基因初级转录本的可变剪接产生的 FN 异构体。它在肿瘤基质和新生肿瘤血管系统上表达，而在正常成人组织中除少数例外情况外均不存在，这暗示了 ED-B FN 具有预后和诊断价值。我们研究了 ED-B FN 的定位和来源，因为这对于理解其在肿瘤发展中的作用以及设计针对该分子的策略都具有重要意义。我们已经证实，ED-B FN 在大多数乳腺癌和结直肠癌组织样本中表达，肿瘤细胞周围和肿瘤基质中有强烈的免疫组织化学染色。未观察到肿瘤新生血管的染色。通过逆转录聚合酶链反应检测发现，一系列肿瘤细胞系和内皮细胞系（包括原代细胞和转化细胞）均可产生 ED-B FN，但在质膜上不表达。在肿瘤异种移植中可见人 ED-B FN 的强表达。这些数据表明，肿瘤细胞可作为肿瘤中 ED-B FN 的来源。肿瘤细胞系缺乏细胞表面表达对于针对该分子的治疗策略设计具有明确的意义。
