Nackaerts K, Verbeken E, Deneffe G, Vanderschueren B, Demedts M, David G
Center for Human Genetics and Flanders Interuniversity for Biotechnology, University of Leuven, Belgium.
Int J Cancer. 1997 Jun 20;74(3):335-45. doi: 10.1002/(sici)1097-0215(19970620)74:3<335::aid-ijc18>3.0.co;2-a.
Heparan sulfate (HS) functions as a co-factor in several signal-transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung-cancer tissues and assayed for the presence of HSPGs in extracts of human lung-cancer cell lines, using a panel of native HS-, delta-HS- and HSPG (syndecan, glypican, CD44 and perlecan) core protein-specific monoclonal antibodies. Compared to normal epithelia, non-small-cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface-associated HSPGs (most consistently of syndecan-1). CD44 or CD44-variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix-associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous-cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for delta-HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and delta-HS reactions. Marked differences in HSPG expression also were observed among various non-small-cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype.
硫酸乙酰肝素（HS）在影响细胞生长、分化、黏附和运动的多个信号转导系统中作为辅因子发挥作用。因此，HS也可能在细胞的恶性转化、肿瘤生长、细胞侵袭和肿瘤转移形成中发挥作用。为了探究这一假说，我们使用一组天然HS、δ - HS和HSPG（syndecan、glypican、CD44和perlecan）核心蛋白特异性单克隆抗体，分析了人肺癌组织切片中HS和硫酸乙酰肝素蛋白聚糖（HSPG）的表达，并检测了人肺癌细胞系提取物中HSPG的存在情况。与正常上皮相比，非小细胞肺癌，尤其是低分化肿瘤，通常表达减少的主要细胞表面相关HSPG（最一致的是syndecan - 1）。相比之下，在所有肿瘤细胞上都发现了CD44或CD44变体蛋白，无论其分化程度如何。Perlecan是一种在正常支气管上皮基底膜中发现的与基质相关的HSPG，在侵袭性支气管源性癌中始终检测不到。在肺鳞状细胞癌中，与基质接触的细胞以及这些肿瘤分化较差的区域中，天然HS的染色反应始终减少。然而，δ - HS的反应并未减少，这表明这些肿瘤细胞的HS发生了结构变化。相比之下，低分化腺癌产生强烈的HS和δ - HS反应。在各种非小细胞肺癌细胞系中也观察到HSPG表达的显著差异。我们的结果表明，低分化肺肿瘤的HSPG表达模式发生了明显改变，这可能有助于其侵袭性表型的形成。
