Abe Anna, Nagatsuma Akiko Kawano, Higuchi Youichi, Nakamura Yuka, Yanagihara Kazuyoshi, Ochiai Atsushi
Laboratory of Cancer Biology, Department of Integrated Bioscience, Graduate School of Frontier Science, University of Tokyo, Kashiwa, Chiba, Japan.
Pathology Division, Exploratory Oncology Research and Clinical Trial Center, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Gastric Cancer. 2017 Jan;20(1):92-103. doi: 10.1007/s10120-015-0584-y. Epub 2015 Dec 22.
Fibroblasts are the commonest type of cancer stromal cells. Inflammation occurs in cancer tissue, and the inflammatory process has been suggested to be caused by interactions between immune cells and cancer cells. In this study, we clarified that site-specific fibroblasts regulate the formation of a site-specific inflammatory niche according to the depth of gastric cancer cell invasion.
Immunohistochemistry was performed with paraffin-embedded tissues. The numbers of immune cells and the fibroblast area were calculated according to the cancer depth. The gene expression patterns of submucosal fibroblasts and subperitoneal fibroblasts stimulated with HSC44PE-conditioned medium were analyzed with a microarray. To examine the effects on the cancer microenvironment of differences in gene expressions between HSC44PE-stimulated submucosal fibroblasts and subperitoneal fibroblasts, assays of HSC44PE proliferation, T cell migration, and M2-like macrophage differentiation were performed.
The distributions of immune cells differed between the submucosal layer and the subserosal layer. The number of M2 macrophages was significantly higher and the fibroblast area was significantly larger in the subserosal layer compared with the submucosal layer. High expression levels of IL1B, TNFSF15, and CCL13 were observed in HSC44PE-stimulated submucosal fibroblasts, and higher expression levels of TGFB2, CSF1, CCL8, and CXCL5 were found in HSC44PE-stimulated subperitoneal fibroblasts. HSC44PE-stimulated subperitoneal fibroblast medium promoted the differentiation of monocytes into M2-like macrophages, whereas HSC44PE-stimulated submucosal fibroblasts significantly induced the migration of Jurkat cells and the growth of HSC44PE cells.
The dynamic states of immune cells differ between the submucosal and subserosal layers in cancer tissues. Site-specific fibroblasts regulate site-specific inflammatory niche formation according to the depth of cancer cell invasion.
成纤维细胞是癌基质细胞中最常见的类型。癌症组织中会发生炎症，且炎症过程被认为是由免疫细胞与癌细胞之间的相互作用引起的。在本研究中，我们阐明了位点特异性成纤维细胞根据胃癌细胞侵袭深度调节位点特异性炎症微环境的形成。
对石蜡包埋组织进行免疫组织化学分析。根据癌症深度计算免疫细胞数量和成纤维细胞面积。用微阵列分析经HSC44PE条件培养基刺激的黏膜下成纤维细胞和腹膜下成纤维细胞的基因表达模式。为检测HSC44PE刺激的黏膜下成纤维细胞和腹膜下成纤维细胞之间基因表达差异对癌症微环境的影响，进行了HSC44PE增殖、T细胞迁移和M2样巨噬细胞分化的检测。
黏膜下层和浆膜下层的免疫细胞分布不同。与黏膜下层相比，浆膜下层的M2巨噬细胞数量显著更高，成纤维细胞面积显著更大。在HSC44PE刺激的黏膜下成纤维细胞中观察到IL1B、TNFSF15和CCL13的高表达水平，而在HSC44PE刺激的腹膜下成纤维细胞中发现TGFB2、CSF1、CCL8和CXCL5的表达水平更高。HSC44PE刺激的腹膜下成纤维细胞培养基促进单核细胞分化为M2样巨噬细胞，而HSC44PE刺激的黏膜下成纤维细胞显著诱导Jurkat细胞迁移和HSC44PE细胞生长。
癌症组织中黏膜下层和浆膜下层的免疫细胞动态状态不同。位点特异性成纤维细胞根据癌细胞侵袭深度调节位点特异性炎症微环境的形成。
Zotero 插件