Liu Xinlu, Li Na, Zhang Chi, Wu Xiaoyu, Zhang Shoujia, Dong Gang, Liu Ge
1st Department of general surgery, The First Affiliated Hospital of Dalian Medical University, No. 193 Union Road, Dalian City, Liaoning Province, China.
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian City, Liaoning Province, China.
Transl Oncol. 2022 May;19:101389. doi: 10.1016/j.tranon.2022.101389. Epub 2022 Mar 15.
Exosomes are secreted nanovesicles consisting of biochemical molecules, including proteins, RNAs, lipids, and metabolites that play a prominent role in tumor progression. In this study, we performed a label-free proteomic analysis of exosomes from a pair of homologous human colorectal cancer cell line with different metastatic abilities. A total of 115 exoDEPs were identified, with 31 proteins upregulated and 84 proteins downregulated in SW620 exosome. We also detected 30 proteins expressed only in SW620 exosomes and 60 proteins expressed only in SW480 exosomes. Bioinformatics analysis enriched the components and pathways associated with the extracellular matrix, cytoskeleton-related pathways, and immune system changes of colorectal cancer (CRC). Cellular function experiments confirmed the role of SW620 exosomes in promoting the proliferation, migration, and invasion of SW480 cells. Further verifications were performed on six upregulated exoDEPs (FGFBP1, SIPA1, THBS1, TGFBI, COL6A1, and RPL10), three downregulated exoDEPs (SLC2A3, MYO1D, and RBP1), and three exoDEPs (SMOC2, GLG1, and CEMIP) expressed only in SW620 by WB and IHC. This study provides a complete and novel basis for exploring new drug targets to inhibit the invasion and metastasis of CRC.
外泌体是由生物化学分子组成的分泌性纳米囊泡，这些分子包括蛋白质、RNA、脂质和代谢产物，它们在肿瘤进展中发挥着重要作用。在本研究中，我们对一对具有不同转移能力的同源人类结肠癌细胞系的外泌体进行了无标记蛋白质组学分析。共鉴定出115种外泌体差异表达蛋白（exoDEP），其中31种蛋白在SW620外泌体中上调，84种蛋白下调。我们还检测到30种仅在SW620外泌体中表达的蛋白和60种仅在SW480外泌体中表达的蛋白。生物信息学分析丰富了与细胞外基质、细胞骨架相关途径以及结直肠癌（CRC）免疫系统变化相关的成分和途径。细胞功能实验证实了SW620外泌体在促进SW480细胞增殖、迁移和侵袭中的作用。通过蛋白质免疫印迹（WB）和免疫组织化学（IHC）对6种上调的exoDEP（FGFBP1、SIPA1、THBS1、TGFBI、COL6A1和RPL10）、3种下调的exoDEP（SLC2A3、MYO1D和RBP1）以及3种仅在SW620中表达的exoDEP（SMOC2、GLG1和CEMIP）进行了进一步验证。本研究为探索抑制CRC侵袭和转移的新药物靶点提供了完整而新颖的依据。
