Nugteren Sandrine, Goos Jeroen A C M, Delis-van Diemen Pien M, Simons-Oosterhuis Ytje, Lindenbergh-Kortleve Dicky J, van Haaften Daniëlle H, Sanders Joyce, Meijer Gerrit A, Fijneman Remond J A, Samsom Janneke N
Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, The Netherlands.
Departments of Clinical Neuroscience, Radiopharmacy, and Oncology & Pathology, Karolinska Institute, Stockholm, Sweden.
Oncoimmunology. 2020 Oct 13;9(1):1832761. doi: 10.1080/2162402X.2020.1832761.
Secretory leukocyte protease inhibitor (SLPI), a pleiotropic protein expressed by healthy intestinal epithelial cells, functions as an inhibitor of NF-κB and neutrophil proteases and exerts antimicrobial activity. We previously showed SLPI suppresses intestinal epithelial chemokine production in response to microbial contact. Increased SLPI expression was recently detected in various types of carcinoma. In addition, accumulating evidence indicates SLPI expression is favorable for tumor cells. In view of these findings and the abundance of SLPI in the colonic epithelium, we hypothesized SLPI promotes colorectal cancer (CRC) growth and metastasis. Here, we aimed to establish whether SLPI expression in CRC is related to clinical outcome. Using a cohort of 507 patients with CRC who underwent resection of liver metastases, we show that high SLPI protein expression in both liver metastases and primary CRC is associated with significantly shorter overall survival after resection of liver metastases. The prognostic value of SLPI in CRC patients with liver metastases implies a role for SLPI in the formation of metastasis of human CRC. Based on the immune regulatory functions of SLPI, we anticipate that expression of SLPI provides tumors with a mechanism to evade infiltration by immune cells.
分泌型白细胞蛋白酶抑制剂（SLPI）是一种由健康肠道上皮细胞表达的多效性蛋白，它作为核因子κB（NF-κB）和中性粒细胞蛋白酶的抑制剂发挥作用，并具有抗菌活性。我们之前发现，SLPI可抑制肠道上皮细胞在接触微生物时产生趋化因子。最近在各类癌症中均检测到SLPI表达增加。此外，越来越多的证据表明，SLPI表达对肿瘤细胞有利。鉴于这些发现以及结肠上皮中SLPI的丰富表达，我们推测SLPI会促进结直肠癌（CRC）的生长和转移。在此，我们旨在确定CRC中SLPI的表达是否与临床结果相关。通过对507例行肝转移灶切除的CRC患者进行队列研究，我们发现肝转移灶和原发性CRC中SLPI蛋白的高表达均与肝转移灶切除术后的总生存期显著缩短相关。SLPI在伴有肝转移的CRC患者中的预后价值表明，SLPI在人类CRC转移形成中发挥作用。基于SLPI的免疫调节功能，我们预计SLPI的表达为肿瘤提供了一种逃避免疫细胞浸润的机制。
