Department of Molecular Pathophysiology, Kyungpook National University College of Pharmacy, Daegu, Korea.
Department of Pathology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
Korean J Gastroenterol. 2022 Apr 25;79(4):170-176. doi: 10.4166/kjg.2022.008.
BACKGROUND/AIMS: Angiogenesis is essential for the outgrowth and metastasis of tumors. The structure and characteristics of tumor vasculature differ from those of normal vessels. We compared the characteristics of differentially expressed genes in endothelial cells (ECs) isolated from gastric and normal cells.
Previously, we had isolated pure tumor ECs (TECs) and normal ECs (NECs) from advanced gastric cancer (AGC) lesions and normal mucosal tissues, respectively. Using the oligomer chip platform of the Affymetrix GeneChip technology, genes that were expressed more than three-fold with a significance of p≤0.001 were measured. The intercellular adhesion molecule 1 (ICAM-1) was found to be overexpressed in the TECs compared to the normal gastric ECs. In this study, the upregulation of ICAM-1 was confirmed in cultured TECs by immunofluorescence.
The expression of ICAM-1 was upregulated in the ECs, as well as in the stromal and immune cells, in early human gastric preneoplastic and hepatic fibrotic tissues. Upregulation of ICAM-1 was observed in the TECs, immune cells, and cancer epithelial cells in AGC and hepatocellular carcinoma (HCC). These results suggest that increased ICAM-1 expression in the ECs of the tissue microenvironment progressively contributes to the recruitment of immune cells to promote inflammation, leading to fibrosis and tumorigenesis.
Therefore, upregulated ICAM-1 in the tissues in premalignant gastric diseases or hepatic fibrosis and their malignant cancers could be a promising target for disease prevention and treatment.
背景/目的：血管生成对于肿瘤的生长和转移至关重要。肿瘤血管的结构和特征与正常血管不同。我们比较了从胃癌病变和正常黏膜组织中分离出的内皮细胞（EC）中差异表达基因的特征。
此前，我们已经从晚期胃癌（AGC）病变和正常黏膜组织中分别分离出了纯肿瘤 EC（TEC）和正常 EC（NEC）。使用 Affymetrix GeneChip 技术的寡聚物芯片平台，测量了表达倍数超过 3 倍且 p 值≤0.001 的基因。与正常胃 EC 相比，TEC 中细胞间黏附分子 1（ICAM-1）表达过度。在这项研究中，通过免疫荧光证实了培养的 TEC 中 ICAM-1 的上调。
在人胃前病变和肝纤维化组织中，EC 以及基质和免疫细胞中 ICAM-1 的表达上调。在 AGC 和肝细胞癌（HCC）中，TEC、免疫细胞和癌细胞上皮细胞中观察到 ICAM-1 的上调。这些结果表明，组织微环境中 EC 中 ICAM-1 的表达上调逐渐导致免疫细胞的募集，从而促进炎症、纤维化和肿瘤发生。
因此，在癌前胃疾病或肝纤维化及其恶性肿瘤组织中上调的 ICAM-1 可能是疾病预防和治疗的有前途的靶点。
