背景:动态的细胞-细胞相互作用塑造肿瘤微环境以调节肿瘤生长和侵袭性。肌成纤维细胞是在结直肠癌(CRC)中上调的胃肠道基质细胞,可能在肿瘤-基质细胞通讯中起重要作用。血管生成素是一种14kDa核糖核酸酶,可调节成肌纤维细胞的功能,并与小鼠模型中的成肌纤维细胞-CRC细胞通讯有关。然而,它在人类患者中的作用还没有得到很好的证实。
方法:开放访问,配对的正常人结肠和CRC组织的注释单细胞RNA测序数据可在国家生物技术信息中心基因表达综合数据库中获得。我们通过分析来自一组独立配对的正常人结肠和CRC组织的scRNA-seq数据来补充和验证这些数据。CellChat用于从scRNA-seq数据定量推断生物学上有意义的细胞-细胞通讯网络。PLXNB2和α-2肌动蛋白(ACTA2)是调节血管生成素信号传导的细胞表面血管生成素受体。涉及血管生成素的配体-受体相互作用,在每个样品中的细胞群体之间分析PLXNB2和ACTA2。
结果:我们发现与正常结肠和CRC组织相比,血管生成素的整体表达没有差异。在正常结肠组织中,肌成纤维细胞不表达血管生成素或PLXNB2受体。在儿童权利委员会面前,周围基质内的成肌纤维细胞数量显著增加.CRC相关的肌成纤维细胞的特征是血管生成素和PLXNB2受体表达显著上调(P<0.05)。而ACTA2未见差异。CRC细胞不仅使用血管生成素进行自分泌信号传导,而且还通过PLXNB2受体与肌成纤维细胞通信。
结论:与正常人结肠组织相比,CRC组织与肌成纤维细胞的富集相关,肌成纤维细胞表现出血管生成素和血管生成素受体PLXNB2的上调表达。CRC细胞通过血管生成素参与自分泌信号传导,并通过PLXNB2与肌成纤维细胞进行旁分泌信号传导。血管生成素似乎直接参与人类CRC组织中的肿瘤-基质细胞通讯,并且可能在疾病进展中起重要作用。
BACKGROUND: Dynamic cell-cell interactions shape the tumor microenvironment to regulate tumor growth and invasiveness. Myofibroblasts are gastrointestinal stromal cells that are upregulated in the setting of colorectal cancer (CRC) and may play an important role in tumor-stromal cell communication.
Angiogenin is a 14-kDa ribonuclease that regulates myofibroblast function and has been implicated in myofibroblast-CRC cell communication in mouse models. However, its role in human patients has not been well established.
METHODS: Open access, annotated single-cell RNA sequencing data of paired normal human colon and CRC tissue were available in the National Center for Biotechnology Information Gene Expression Omnibus Database. We supplemented and verified these data by analyzing scRNA-seq data from an independent set of paired normal human colon and CRC tissue. CellChat was used to quantitatively infer biologically meaningful cell-cell communication networks from scRNA-seq data. PLXNB2 and α-2 actin (ACTA2) are cell surface
angiogenin receptors that regulate
angiogenin signaling. Ligand-receptor interactions involving angiogenin, PLXNB2, and ACTA2 were analyzed between cell populations in each sample.
RESULTS: We found no difference in overall angiogenin expression comparing normal colon and CRC tissue. In normal colon tissue, myofibroblasts do not express
angiogenin or the PLXNB2 receptor. In the presence of CRC, there was a striking increase in the number of myofibroblast cells within the surrounding stroma. CRC-associated myofibroblasts were characterized by a significant upregulation of both
angiogenin and PLXNB2 receptor expression (P < 0.05), while no difference was seen in ACTA2. CRC cells not only use angiogenin for autocrine signaling but also communicate with myofibroblasts via the PLXNB2 receptor.
CONCLUSIONS: Compared to normal human colon tissue, CRC tissue is associated with an enrichment of myofibroblasts that exhibit upregulated expression of angiogenin and the
angiogenin receptor PLXNB2. CRC cells engage in autocrine signaling via angiogenin and paracrine signaling with myofibroblasts via PLXNB2. Angiogenin appears to be directly involved in tumor-stromal cell communication in human CRC tissue and may play an important role in disease progression.