Circulating peptidome to indicate the tumor-resident proteolysis

Area of Science:

• Biochemistry
• Oncology
• Proteomics

Background:

• Tumor-resident proteases (TRPs) are crucial biomarkers for cancer staging and treatment evaluation.
• Current clinical methods rely on invasive biopsies, limiting monitoring capabilities.

Purpose of the Study:

• To identify circulating peptides produced by TRPs for monitoring anti-cancer treatment efficacy.
• To evaluate the potential of these peptides as noninvasive biomarkers.

Main Methods:

• Established a mouse model for ovarian cancer with drug-resistant HeyA8-MDR cells.
• Administered porous silicon particle- or multistage vector (MSV)-enabled EphA2 siRNA therapy.
• Utilized immunohistochemistry and ex vivo proteolysis assays to analyze protease activity and peptide generation.

Main Results:

• Decreased matrix metallopeptidase 9 (MMP-9) expression was observed in responsive tumors.
• C3f peptides were identified as substrates cleaved by MMP-9 into specific fragments.
• Circulating C3f fragments in serum were primarily derived from tumor-resident MMP-9 activity.

Conclusions:

• Circulating C3f-derived peptides can serve as noninvasive biomarkers for evaluating anti-cancer treatment efficacy.
• This proteomics approach offers a user-friendly method for monitoring therapeutic responses.
• Tumor-resident protease activity can be assessed through circulating peptide fragments.