3447Colorado State University, Fort Collins, CO, USA.
Ethos Diagnostic Science, Wheat Ridge, CO, USA.
Vet Pathol. 2021 Sep;58(5):981-993. doi: 10.1177/0300985821996671. Epub 2021 Mar 9.
Periostin is a matricellular protein important in regulating bone, tooth, and cardiac development. In pathologic conditions, periostin drives allergic and fibrotic inflammatory diseases and is also overexpressed in certain cancers. Periostin signaling in tumors has been shown to promote angiogenesis, metastasis, and cancer stem cell survival in rodent models, and its overexpression is associated with poor prognosis in human glioblastoma. However, the role of periostin in regulating tumorigenesis of canine cancers has not been evaluated. Given its role in bone development, we sought to evaluate mRNA and protein expression of periostin in canine osteosarcoma (OS) and assess its association with patient outcome. We validated an anti-human periostin antibody cross-reactive to canine periostin via western blot and immunohistochemistry and evaluated periostin expression in microarray data from 49 primary canine OS tumors and 8 normal bone samples. Periostin mRNA was upregulated greater than 40-fold in canine OS tumors compared to normal bone and was significantly correlated with periostin protein expression based on quantitative image analysis. However, neither periostin mRNA nor protein expression were associated with time to metastasis in this cohort. Gene Set Enrichment Analysis demonstrated significant enhancement of pro-tumorigenic pathways including canonical signaling, epithelial-mesenchymal transition, and angiogenesis in periostin-high tumors, while periostin-low tumors demonstrated evidence of heightened antitumor immune responses. Overall, these data identify a novel antibody that can be used as a tool for evaluation of periostin expression in dogs and suggest that investigation of pathway-targeted drugs in periostin overexpressing canine OS may be a potential therapeutic target.
纤调蛋白是一种细胞外基质蛋白，在调控骨骼、牙齿和心脏发育方面发挥着重要作用。在病理条件下，纤调蛋白可驱动过敏和纤维化炎症性疾病，并在某些癌症中过度表达。在啮齿动物模型中，纤调蛋白在肿瘤中的信号传递被证明可促进血管生成、转移和癌症干细胞存活，其过表达与人类胶质母细胞瘤的预后不良相关。然而，纤调蛋白在调控犬类癌症的肿瘤发生中的作用尚未得到评估。鉴于其在骨骼发育中的作用，我们试图评估纤调蛋白在犬骨肉瘤（OS）中的 mRNA 和蛋白表达，并评估其与患者预后的关系。我们通过 Western blot 和免疫组织化学验证了一种抗人纤调蛋白抗体与犬纤调蛋白的交叉反应性，并评估了 49 例原发性犬 OS 肿瘤和 8 例正常骨样本的微阵列数据中的纤调蛋白表达。与正常骨相比，犬骨肉瘤肿瘤中纤调蛋白 mRNA 的上调超过 40 倍，且基于定量图像分析，与纤调蛋白蛋白表达呈显著相关性。然而，在该队列中，纤调蛋白 mRNA 或蛋白表达均与转移时间无相关性。基因集富集分析表明，在纤调蛋白高表达的肿瘤中，促肿瘤发生途径（包括经典信号通路、上皮-间充质转化和血管生成）显著增强，而纤调蛋白低表达的肿瘤则表现出增强的抗肿瘤免疫反应的证据。总体而言，这些数据确定了一种新型抗体，可作为评估犬纤调蛋白表达的工具，并表明在纤调蛋白过表达的犬骨肉瘤中研究 途径靶向药物可能是一种潜在的治疗靶点。
