Skandalis Spyros S, Theocharis Achilleas D, Vynios Demitrios H, Papageorgakopoulou Nickoletta, Hjerpe Anders, Karamanos Nikos K, Theocharis Dimitrios A
Laboratory of Biochemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Department of Chemistry, University of Patras, 26500 Patras, Greece.
Biochim Biophys Acta. 2006 Jul;1760(7):1046-53. doi: 10.1016/j.bbagen.2006.02.007. Epub 2006 Mar 9.
Aggrecan is a key component of cartilage and is responsible for the integrity and function of the tissue. In this study, the content of aggrecan and its structural modifications in adjacent to cancer apparently normal cartilages (AANCs) from various stages of laryngeal squamous cell carcinoma (LSCC) were investigated. Our data demonstrated a stage-related loss of aggregable aggrecan in AANCs, compared to the healthy laryngeal cartilage (HLC), which was excessive in advanced stages of disease. On aggregable aggrecan level, AANCs were characterized by significant compositional and structural modifications, the extent of which was closely related with the stage of LSCC. Four concrete subpopulations of aggregable molecules with particular physicochemical characteristics were identified with a strong tendency to prevail subpopulations of molecules of lower hydrodynamic sizes with increasing LSCC stage. These findings demonstrated that the cleavage of aggregable aggrecan occurred in concrete peptide bonds within the CS-1 and CS-2 attachment domains. These significant alterations were closely associated with the process of cartilage destruction, indicating the crucial role of aggrecan during LSCC.
聚集蛋白聚糖是软骨的关键成分,负责组织的完整性和功能。在本研究中,我们调查了来自不同阶段喉鳞状细胞癌(LSCC)的癌旁看似正常软骨(AANC)中聚集蛋白聚糖的含量及其结构修饰。我们的数据表明,与健康喉软骨(HLC)相比,AANC中可聚集的聚集蛋白聚糖出现与阶段相关的损失,在疾病晚期这种损失更为严重。在可聚集的聚集蛋白聚糖水平上,AANC具有显著的组成和结构修饰,其程度与LSCC的阶段密切相关。我们鉴定出了具有特定物理化学特征的可聚集分子的四个具体亚群,随着LSCC阶段的增加,具有较低流体动力学尺寸的分子亚群有占主导地位的强烈趋势。这些发现表明,可聚集的聚集蛋白聚糖的切割发生在CS-1和CS-2附着域内的特定肽键处。这些显著变化与软骨破坏过程密切相关,表明聚集蛋白聚糖在LSCC过程中起关键作用。