Abstract：
Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%; p = 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (p = 0.0031) and distant organ metastasis (p < 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.
摘要：
癌症相关成纤维细胞（CAF）的肿瘤支持能力的证据已迅速积累。揭示骨膜素(POSTN)在结直肠癌(CRC)中表达的临床病理意义,本研究免疫组织化学检查了其表达状态。此外，为了揭示其相关机制，进行了分子实验。在CRC组织中，44%的病例(119/269)在CAF中表现出POSTN表达。相比之下,CRC细胞以几乎不可检测的水平表达POSTN。生存分析发现，POSTN阳性CRC患者的5年生存率明显更差（63.2%vs.81.2%；p=0.011）。单因素分析显示POSTN阳性与腹膜转移(p=0.0031)和远处器官转移(p<0.001)相关。此外，免疫组织化学分析确定了CRC细胞中POSTN和p53完全丢失状态之间的显著关联。CAFs中Decorin和成纤维细胞活化蛋白的表达也与POSTN相关。POSTN显着增强了FAK和AKT或STAT3激活的CRC细胞和成纤维细胞的迁移，和共培养试验证明了CRC细胞和成纤维细胞之间的通讯，这增强了成纤维细胞中的STAT3激活。根据我们的结果，我们推测基质POSTN通过基质重塑能力加速转移，并激活肿瘤和基质细胞的迁移。
