Colorectal Cancer-Associated Myofibroblasts Exhibit Enhanced Angiogenin Expression and Signaling via the PLXNB2...

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Colorectal cancer (CRC) progression involves complex interactions within the tumor microenvironment.
• Myofibroblasts, activated stromal cells, are implicated in CRC growth and invasiveness.
• Angiogenin, a ribonuclease, influences myofibroblast function and tumor-stromal communication, but its role in human CRC is unclear.

Purpose of the Study:

• To investigate the role of angiogenin and its receptors in human colorectal cancer (CRC) tumor-stromal communication.
• To analyze cell-cell interactions between cancer cells and myofibroblasts in the context of CRC.
• To determine if angiogenin signaling is altered in human CRC tissue compared to normal colon tissue.

Main Methods:

• Utilized single-cell RNA sequencing (scRNA-seq) data from paired normal human colon and CRC tissues.
• Employed CellChat software to infer cell-cell communication networks from scRNA-seq data.
• Analyzed ligand-receptor interactions involving angiogenin, PLXNB2, and ACTA2 in different cell populations.

Main Results:

• Found no significant difference in overall angiogenin expression between normal and CRC tissues.
• Observed a marked increase in myofibroblast numbers in CRC tissue, with upregulation of angiogenin and its receptor PLXNB2.
• CRC cells exhibit autocrine angiogenin signaling and paracrine communication with myofibroblasts via PLXNB2.

Conclusions:

• Human CRC tissue shows an enrichment of myofibroblasts expressing angiogenin and PLXNB2.
• Angiogenin mediates both autocrine signaling in CRC cells and paracrine signaling with myofibroblasts.
• Angiogenin plays a direct role in tumor-stromal communication and may be a key factor in colorectal cancer progression.