Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal...

Area of Science:

• Oncology
• Cell Biology
• Biomarker Discovery

Background:

• Cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC) stroma correlate with poor prognosis.
• CAF-cancer cell interactions, mediated by factors like TGF-β1, drive CRC progression and aggressive phenotypes.
• Existing CAF biomarkers exhibit limited specificity and heterogeneous expression.

Purpose of the Study:

• To evaluate Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) as potential biomarkers for fibroblast activation.
• To determine the role of AOC3 and LRRC17 in predicting colorectal cancer (CRC) progression.

Main Methods:

• Immunofluorescence staining of AOC3, LRRC17, and α-SMA in myofibroblasts, CAFs, and normal fibroblasts (NFs).
• Assessment of cell proliferation (MTT assay) and contractility (collagen gel assay) under various conditions, including TGF-β1 treatment.
• Comparison of fluorescence intensity and functional assays between different fibroblast types and treatment groups.

Main Results:

• AOC3, LRRC17, and α-SMA were expressed in colonic fibroblasts, notably higher in CAFs.
• TGF-β1 treatment led to significant downregulation of AOC3 and upregulation of LRRC17 and α-SMA.
• Fibroblasts showed increased proliferation and contractility, particularly NFs under complete medium and TGF-β1 stimulation.

Conclusions:

• AOC3 and LRRC17 demonstrate potential as reliable markers for CAF activation.
• These emerging biomarkers may be valuable in understanding and predicting colorectal cancer (CRC) progression.