Korpetinou Angeliki, Skandalis Spyros S, Moustakas Aristidis, Happonen Kaisa E, Tveit Heidi, Prydz Kristian, Labropoulou Vassiliki T, Giannopoulou Efstathia, Kalofonos Haralambos P, Blom Anna M, Karamanos Nikos K, Theocharis Achilleas D
Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
PLoS One. 2013 Oct 31;8(10):e78157. doi: 10.1371/journal.pone.0078157. eCollection 2013.
Serglycin is a proteoglycan expressed by some malignant cells. It promotes metastasis and protects some tumor cells from complement system attack. In the present study, we show for the first time the in situ expression of serglycin by breast cancer cells by immunohistochemistry in patients' material. Moreover, we demonstrate high expression and constitutive secretion of serglycin in the aggressive MDA-MB-231 breast cancer cell line. Serglycin exhibited a strong cytoplasmic staining in these cells, observable at the cell periphery in a thread of filaments near the cell membrane, but also in filopodia-like structures. Serglycin was purified from conditioned medium of MDA-MB-231 cells, and represented the major proteoglycan secreted by these cells, having a molecular size of ~ 250 kDa and carrying chondroitin sulfate side chains, mainly composed of 4-sulfated (~ 87%), 6-sulfated (~ 10%) and non-sulfated (~ 3%) disaccharides. Purified serglycin inhibited early steps of both the classical and the lectin pathways of complement by binding to C1q and mannose-binding lectin. Stable expression of serglycin in less aggressive MCF-7 breast cancer cells induced their proliferation, anchorage-independent growth, migration and invasion. Interestingly, over-expression of serglycin lacking the glycosaminoglycan attachment sites failed to promote these cellular functions, suggesting that glycanation of serglycin is a pre-requisite for its oncogenic properties. Our findings suggest that serglycin promotes a more aggressive cancer cell phenotype and may protect breast cancer cells from complement attack supporting their survival and expansion.
丝甘素是一种由某些恶性细胞表达的蛋白聚糖。它促进转移，并保护一些肿瘤细胞免受补体系统攻击。在本研究中，我们首次通过免疫组织化学在患者材料中显示了乳腺癌细胞原位表达丝甘素。此外，我们证明了侵袭性MDA-MB-231乳腺癌细胞系中丝甘素的高表达和组成型分泌。丝甘素在这些细胞中表现出强烈的细胞质染色，在细胞膜附近的细丝状结构中可在细胞周边观察到，也存在于丝状伪足样结构中。丝甘素从MDA-MB-231细胞的条件培养基中纯化得到，是这些细胞分泌的主要蛋白聚糖，分子大小约为250 kDa，带有硫酸软骨素侧链，主要由4-硫酸化（约87%）、6-硫酸化（约10%）和非硫酸化（约3%）二糖组成。纯化的丝甘素通过与C1q和甘露糖结合凝集素结合，抑制补体经典途径和凝集素途径的早期步骤。在侵袭性较弱的MCF-7乳腺癌细胞中稳定表达丝甘素可诱导其增殖、非贴壁生长、迁移和侵袭。有趣的是，缺乏糖胺聚糖附着位点的丝甘素过表达未能促进这些细胞功能，这表明丝甘素的糖基化是其致癌特性的先决条件。我们的研究结果表明，丝甘素促进更具侵袭性的癌细胞表型，并可能保护乳腺癌细胞免受补体攻击，支持其存活和扩增。
