A. Hu1, J. Mitchem2, Y. Nussbaum2, J. Yoo1 1Brigham And Women’s Hospital, General And GI / Surgery, Boston, MA, USA 2University Of Missouri, Surgery, Columbia, MO, USA
Introduction: 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 colorectal cancer tissue (n=20) was available in the NCBI Gene Expression Omnibus Database. CellChat was utilized to quantitatively infer biologically meaningful cell-cell communication networks from scRNA-seq data. PLXNB2 and 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. However, notable differences were identified in the types of cells that express angiogenin, with a shift in angiogenin expression from the stroma under normal conditions to the epithelium in the presence of cancer. In normal colon, myofibroblasts do not express angiogenin or the PLXNB2 receptor. Despite an overall decrease in angiogenin expression in the 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 utilize angiogenin for autocrine signaling but also to communicate with myofibroblasts via the PLXNB2 receptor (P<0.05) and ACTA2 (P=0.0647).
Conclusion: Compared to normal human colon tissue, CRC 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, as well as paracrine signaling with myofibroblasts via PLXNB2. Angiogenin is directly involved in tumor-stromal cell communication in human colon tissue and may play an important role in colorectal cancer progression.