Tellez-Gabriel Marta, Tekpli Xavier, Reine Trine M, Hegge Beate, Nielsen Stephanie R, Chen Meng, Moi Line, Normann Lisa Svartdal, Busund Lill-Tove R, Calin George A, Mælandsmo Gunhild M, Perander Maria, Theocharis Achilleas D, Kolset Svein O, Knutsen Erik
Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Front Oncol. 2022 Apr 14;12:868868. doi: 10.3389/fonc.2022.868868. eCollection 2022.
Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, and it is a significant EMT marker gene. We further find that serglycin is more expressed by breast cancer cell lines with a mesenchymal phenotype as well as the basal-like subtype of breast cancers. By examining immune staining and single cell sequencing data of breast cancer tissue, we show that serglycin is highly expressed by infiltrating immune cells in breast tumor tissue.
丝甘蛋白聚糖是一种由免疫细胞高度表达的蛋白聚糖,其功能与趋化因子、蛋白酶、组胺、生长因子及其他生物活性分子的储存、分泌、运输和保护有关。近年来,已证明丝甘蛋白聚糖也由其他几种细胞类型表达,如内皮细胞、肌肉细胞和多种癌细胞。在此,我们表明在转化生长因子β(TGF-β)诱导的上皮-间质转化(EMT)中丝甘蛋白聚糖表达上调。功能研究提供了证据表明丝甘蛋白聚糖在上皮和间质表型之间的转变调节中起重要作用,并且它是一个重要的EMT标记基因。我们进一步发现丝甘蛋白聚糖在具有间质表型的乳腺癌细胞系以及乳腺癌的基底样亚型中表达更高。通过检查乳腺癌组织的免疫染色和单细胞测序数据,我们表明丝甘蛋白聚糖在乳腺肿瘤组织中的浸润免疫细胞中高度表达。