Broers J L, Rot M K, Oostendorp T, Bepler G, De Leij L, Carney D N, Vooijs G P, Ramaekers F C
Department of Pathology, University Hospital Nijmegen, The Netherlands.
J Cell Sci. 1988 Sep;91 ( Pt 1):91-108. doi: 10.1242/jcs.91.1.91.
The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings.
细胞系在肺癌临床行为研究及预测中的作用仍存在争议。然而，肺肿瘤细胞培养在这些肿瘤的分子和细胞生物学方面的研究中具有重要价值。特别是在研究主要分化类型（鳞状细胞癌、腺癌、小细胞癌）的特异性特征时，体外研究至关重要。培养了28种肺癌细胞系长达四年，并定期使用一组细胞角蛋白（CK）和神经丝（NF）抗体检测它们的中间丝蛋白（IFP）表达模式。这些研究表明，经典型小细胞肺癌（SCLC）细胞系含有CK8、CK18，偶尔含有CK19，而变异型SCLC细胞系通常不表达CK，但可含有NF。非SCLC细胞系，如鳞状细胞癌和腺癌细胞系，含有CK7（大多数情况下）、CK8、CK18和CK19。在一个变异型SCLC细胞系和一个腺癌细胞系中发现了鳞状细胞分化特有的CK4、CK10和CK13。尽管大多数细胞系在生长特性和IFP表达模式方面保持稳定，但五种肺癌培养物表现出从一种细胞类型向另一种细胞类型的转变，同时伴有IFP表达的变化。观察到从经典型SCLC细胞系向变异型SCLC细胞系的进展，以及从变异型SCLC向重新表达细胞角蛋白的细胞系的转变。在某些情况下，这导致细胞系内甚至单个肿瘤细胞内CK和NF的共表达。这些结果有力地支持了早期的发现，即SCLC细胞系中的CK表达是经典分化类型的可靠标志物，而CK的缺失和NF的存在标志着变异型分化。我们结合先前的组织学研究结果对这些结果进行了讨论。
