Circulating peptidome to indicate the tumor-resident proteolysis

Scientific Reports
Zaian DengTony Y Hu

Abstract

Tumor-resident proteases (TRPs) are regarded as informative biomarkers for staging cancer progression and evaluating therapeutic efficacy. Currently in the clinic, measurement of TRP is dependent on invasive biopsies, limiting their usefulness as monitoring tools. Here we identified circulating peptides naturally produced by TRPs, and evaluated their potential to monitor the efficacy of anti-tumor treatments. We established a mouse model for ovarian cancer development and treatment by orthotopic implantation of the human drug-resistant ovarian cancer cell line HeyA8-MDR, followed by porous silicon particle- or multistage vector (MSV) - enabled EphA2 siRNA therapy. Immunohistochemistry staining of tumor tissue revealed decreased expression of matrix metallopeptidase 9 (MMP-9) in mice exhibiting positive responses to MSV-EphA2 siRNA treatment. We demonstrated, via an ex vivo proteolysis assay, that C3f peptides can act as substrates of MMP-9, which cleaves C3f at L1311-L1312 into two peptides (SSATTFRL and LWENGNLLR). Importantly, we showed that these two C3f-derived fragments detected in serum were primarily generated by tumor-resident, but not blood-circulating, MMP-9. Our results suggested that the presence of the circulating ...Continue Reading

References

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Citations

Nov 13, 2020·Molecular & Cellular Proteomics : MCP·Leandro Xavier NevesAdriana F Paes Leme
Feb 13, 2021·Molecular & Cellular Proteomics : MCP·Leandro Xavier NevesAdriana F Paes Leme
Jan 5, 2021·Protein and Peptide Letters·Mohamed K Al-EssaKamal Al-Hadidi

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Methods Mentioned

BETA
biopsy
enzyme-linked immunosorbent assay
ELISA
transfection
biopsies
cleavage assay
chips
chip

Software Mentioned

Mascot
ExPASy
Proteome Discoverer
FindPept

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