Colorectal Cancer-Associated Myofibroblasts Exhibit Enhanced Angiogenin Expression and Signaling via the PLXNB2 Receptor
Alexander J. Hu1, James Yoo1, Jonathan Mitchem2, Yulia I. Nussbaum2
1Harvard University, Boston MA; 2University of Missouri, Columbia MO
Background: Dynamic cell-cell interactions shape the tumor microenvironment to influence cancer growth. Angiogenin is a 14-kDa ribonuclease that regulates myofibroblast function and has been implicated in myofibroblast-CRC cell communication in mouse models. Its role in human patients is not well established.
Methods: scRNA-seq data of paired normal human colon and CRC tissue (n=20) was available in the NCBI Database. CellChat quantitatively infers biologically meaningful cell-cell communication networks from scRNA-seq data. Ligand-receptor interactions involving angiogenin, PLXNB2 and ACTA2 (angiogenin receptors) were analyzed between cell populations in each sample.
Results: We found no difference in overall angiogenin expression comparing normal colon and CRC tissue. However, there was 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 demonstrated 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 communicate with myofibroblasts via the PLXNB2 receptor (P<0.05) and ACTA2 (P=0.0647).
Conclusion: CRC is associated with an enrichment of myofibroblasts that exhibit upregulated expression of angiogenin and its 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.
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