Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Department of Surgery and Science, Kyushu University Hospital, Fukuoka, Japan.
Cancer Genomics Proteomics. 2021 Jul-Aug;18(4):521-529. doi: 10.21873/cgp.20277.
BACKGROUND/AIM: Peritoneal dissemination (PD) occurs frequently in gastric cancer (GC) and is fatal. The interactions between tumor cells and stromal cells are critical for cancer progression. Our aim was to identify a novel PD-associated gene derived from stromal cells in GC.
Among the candidate PD-associated genes identified in our previous study, we focused on spondin-2 (SPON2), an extracellular matrix-secreted protein. Clinicopathological and prognostic analyses of SPON2 mRNA expression were performed using GC datasets. Localization of SPON2 expression was assessed by immunohistochemistry. In vitro migration assay and immunofluorescence staining were also conducted using GC cell lines.
SPON2 was expressed in and secreted from cancer-associated fibroblasts in GC. High expression of SPON2 in tumor tissues was correlated with PD, tumor size and poor prognosis in GC. The motility of GC cells was increased by treatment with a SPON2 recombinant protein in vitro.
Cancer-associated fibroblast-derived SPON2 may promote PD, in part, by facilitating GC cell motility and serve as a predictive marker for PD in GC.
背景/目的：胃癌（GC）常发生腹膜转移（PD），且死亡率高。肿瘤细胞与基质细胞的相互作用对癌症进展至关重要。我们的目的是鉴定一种源自 GC 基质细胞的新型 PD 相关基因。
在我们之前的研究中确定了候选 PD 相关基因，我们重点关注细胞外基质分泌蛋白——骨连接素-2（SPON2）。使用 GC 数据集进行 SPON2 mRNA 表达的临床病理和预后分析。通过免疫组织化学评估 SPON2 表达的定位。还使用 GC 细胞系进行体外迁移试验和免疫荧光染色。
SPON2 在 GC 中的癌相关成纤维细胞中表达并分泌。肿瘤组织中 SPON2 的高表达与 PD、肿瘤大小和 GC 的不良预后相关。SPON2 重组蛋白体外处理可增加 GC 细胞的迁移能力。
源自癌相关成纤维细胞的 SPON2 可能通过促进 GC 细胞的迁移来促进 PD，其可作为 GC 中 PD 的预测标志物。
