Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan.
Pathol Int. 2020 Dec;70(12):943-952. doi: 10.1111/pin.13027. Epub 2020 Oct 1.
Intelectin-1 (ITLN1) is an adipokine with an anti-inflammatory function that is involved in neoplastic diseases such as pleural mesothelioma and gastric and prostate cancers. However, the expression and function of ITLN1 in colorectal cancer (CRC) remain unknown. To identify novel prognostic markers or therapeutic targets for CRC, we focused on ITLN1 protein. By immunohistochemistry, 87 (59%) of 148 CRC cases showed reduced expression of ITLN1. ITLN1-reduced CRC cases were associated with higher M grades (P = 0.0017) than ITLN1-retained CRC cases. Furthermore, the cases with ITLN1 retained expression tended toward a more favorable prognosis than those with reduced expression. Cell growth of the CRC cell lines transfected with ITLN1 siRNA were greater than those of the negative control cell lines transfected with siRNA. Levels of phosphorylated epidermal growth factor receptor, Erk and Akt were higher in the CRC cells transfected with ITLN1 siRNA than in control cells. Immunohistochemical analysis of human colorectal polyp specimens also revealed a sequential decrease in the expression of ITLN1 through both the conventional adenoma-carcinoma pathway and the serrated pathway. These results indicated that ITLN1 might play an important role in regulating colorectal tumorigenesis.
肠上皮细胞黏附分子 1(ITLN1)是一种具有抗炎功能的脂肪细胞因子,参与间皮瘤、胃癌和前列腺癌等肿瘤性疾病。然而,ITLN1 在结直肠癌(CRC)中的表达和功能仍不清楚。为了鉴定 CRC 的新型预后标志物或治疗靶点,我们关注 ITLN1 蛋白。通过免疫组织化学染色,在 148 例 CRC 病例中,有 87 例(59%)显示 ITLN1 表达降低。与 ITLN1 保留的 CRC 病例相比,ITLN1 降低的 CRC 病例与更高的 M 分级相关(P = 0.0017)。此外,具有 ITLN1 保留表达的病例倾向于比具有降低表达的病例具有更好的预后。转染 ITLN1 siRNA 的 CRC 细胞系的细胞生长大于转染 siRNA 的阴性对照细胞系。转染 ITLN1 siRNA 的 CRC 细胞中磷酸化表皮生长因子受体、Erk 和 Akt 的水平高于对照细胞。对人类结直肠息肉标本的免疫组织化学分析也表明,通过经典的腺瘤-癌途径和锯齿状途径,ITLN1 的表达依次降低。这些结果表明,ITLN1 可能在调节结直肠肿瘤发生中发挥重要作用。