Far Eastern Memorial Hospital, Banqiao District, New Taipei City, Taiwan, 22060.
School of Medicine, Fu Jen Catholic University, Xinzhuang District, New Taipei City, Taiwan, 24205.
Biochem Cell Biol. 2020 Apr;98(2):112-119. doi: 10.1139/bcb-2018-0246. Epub 2019 May 1.
Glycosaminoglycan-modified proteoglycans play important roles in many cell activities, including cell differentiation and stem cell development. Tumor sphere formation ability is one of properties in cancer stem cells (CSCs). The correlation between CSC markers and proteoglycan remains to be clarified. Upon hepatoma sphere formation, expression of CSC markers CD13, CD90, CD133, and CD44, as well the syndecan family protein syndecan-1 (SDC1), increased as analyzed by PCR. Further examination by suppression of CD13 expression showed downregulation of SDC1 and CD44 gene expression, whereas suppression of SDC1 gene expression downregulated CD13 and CD44 gene expression. Suppression of SDC1 gene expression also suppressed sphere development, as analyzed by a novel sphereocrit assay to quantify the level of sphere formation. The heparin disaccharide components, but not those of chondroitin disaccharide, changed with hepatoma sphere development, revealing the increased levels of -sulfation and 2-O-sulfation. These explained the inhibition of hepatoma sphere formation by exogenous heparin. In conclusion, we found that SDC1 affected CSC marker CD13 and CD44 expression. SDC1 proteoglycan and heparin components changed and affected hepatoma sphere development. Application of heparin mimics in reduction of hepatoma stem cells might be possible.
糖胺聚糖修饰的蛋白聚糖在许多细胞活动中发挥重要作用，包括细胞分化和干细胞发育。肿瘤球形成能力是癌症干细胞（CSC）的特性之一。CSC 标志物与蛋白聚糖之间的相关性仍需阐明。通过肝癌球体形成分析发现，CSC 标志物 CD13、CD90、CD133 和 CD44 的表达增加，通过 PCR 分析发现 syndecan 家族蛋白 syndecan-1（SDC1）的表达增加。进一步通过抑制 CD13 的表达进行检查显示，SDC1 和 CD44 基因表达下调，而 SDC1 基因表达的抑制下调 CD13 和 CD44 基因表达。通过新型球体测定法分析球体发育，发现 SDC1 基因表达的抑制也抑制了球体的形成，该方法可定量测定球体形成的水平。肝素二糖成分而不是软骨素二糖成分随肝癌球体的发育而变化，揭示了 -硫酸化和 2-O-硫酸化水平的增加。这解释了外源性肝素抑制肝癌球体形成的原因。总之，我们发现 SDC1 影响 CSC 标志物 CD13 和 CD44 的表达。SDC1 蛋白聚糖和肝素成分发生变化并影响肝癌球体的发育。肝素类似物在减少肝癌干细胞方面的应用可能是可行的。
