Vaz Juan, Ansari Daniel, Sasor Agata, Andersson Roland
From the Departments of *Surgery and †Pathology, Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
Pancreas. 2015 Oct;44(7):1024-35. doi: 10.1097/MPA.0000000000000409.
Pancreatic cancer is a complex and heterogeneous disease that often lacks disease-specific symptoms in early stages. The malignancy is currently the fourth leading cause of cancer-related death in Western countries. In advanced stages, the overall 5-year survival is less than 1% to 2%. Most available treatments lack convincing cost-efficiency determinations and are generally not associated with relevant success rates. Targeting stromal components and stromal depletion is currently becoming an area of extensive research in pancreatic cancer. In this context, a glycoprotein, SPARC (secreted protein acidic and rich in cysteine) appears to play a central role. Still, the role of SPARC in carcinogenesis is controversial because conflicting results have been reported, and the pathways involved in SPARC signaling are not well established. Nonetheless, SPARC is highly expressed in the tumor stroma, principally in peritumoral fibroblasts, and the overexpression of SPARC in this compartment is associated with poorer prognosis. Interestingly, it has been suggested that SPARC present in the tumor stroma could sequester albumin-bound paclitaxel, enhancing the delivery of paclitaxel into the tumor microenvironment. In the present review, we summarize the known associations between SPARC and pancreatic cancer. Moreover, present and future therapies comprising SPARC-targeting are discussed.
胰腺癌是一种复杂的异质性疾病，早期通常缺乏疾病特异性症状。在西方国家，这种恶性肿瘤目前是癌症相关死亡的第四大主要原因。在晚期，总体5年生存率低于1%至2%。大多数现有的治疗方法缺乏令人信服的成本效益评估，而且总体上与相关的成功率无关。靶向基质成分和基质耗竭目前正成为胰腺癌广泛研究的一个领域。在这种背景下，一种糖蛋白，即富含半胱氨酸的酸性分泌蛋白（SPARC）似乎起着核心作用。然而，SPARC在致癌过程中的作用存在争议，因为已报道的结果相互矛盾，且SPARC信号传导所涉及的途径尚未明确确立。尽管如此，SPARC在肿瘤基质中高度表达，主要在肿瘤周围的成纤维细胞中，且该区域中SPARC的过表达与较差的预后相关。有趣的是，有人提出肿瘤基质中的SPARC可能会螯合白蛋白结合型紫杉醇，从而增强紫杉醇向肿瘤微环境的递送。在本综述中，我们总结了SPARC与胰腺癌之间已知的关联。此外，还讨论了目前以及未来针对SPARC的治疗方法。
