Prostate stromal cell proteomics analysis discriminates normal from tumour reactive stromal phenotypes

Area of Science:

• Oncology
• Cell Biology
• Proteomics

Background:

• Prostate cancer stroma contains myofibroblasts that can promote tumor progression.
• Identifying aggressive myofibroblast subtypes is crucial for diagnosis.
• Molecular markers for these aggressive myofibroblasts are currently unknown.

Purpose of the Study:

• To compare protein profiles of normal and diseased prostate stroma.
• To identify molecular hallmarks distinguishing disease-associated myofibroblasts.
• To investigate the functional and proteomic differences induced by soluble TGF-beta and exosome-associated TGF-beta.

Main Methods:

• Proteomic analysis of normal and diseased prostate stroma.
• In vitro stimulation of normal stromal cells with soluble TGF-beta and exosomes.
• Assessment of stromal cell pro-angiogenic influence on endothelial cells.
• Comparative analysis of protein expression profiles.

Main Results:

• Diseased stroma and exosome-stimulated stroma exhibited pro-angiogenic properties, unlike TGF-beta-stimulated stroma.
• Proteomics revealed elevated Transgelin (TAGLN) in disease-associated stroma.
• Soluble TGF-beta stimulation uniquely altered mitochondrial proteins (VDAC1, VDAC2).
• Aldehyde Dehydrogenase (ALDH1A1) decreased in disease stroma compared to normal.

Conclusions:

• A set of proteins can define disease-associated myofibroblasts in prostate cancer.
• Exosome-generated myofibroblasts closely resemble those found in situ in prostate cancer.
• These findings may aid in diagnosing aggressive prostate cancer subtypes.