ArticleJournal of experimental & clinical cancer research : CR2019
Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Unveiling diagnostic biomarkers and therapeutic targets in lung adenocarcinoma using bioinformatics and experimental validation.Scientific reports · 2025Article
- Environmental pollutant Di-(2-ethylhexyl) phthalate induces asthenozoospermia: new insights from network toxicology.Molecular diversity · 2025Article
- Article
- Surface Proteome of Extracellular Vesicles and Correlation Analysis Reveal Breast Cancer Biomarkers.Cancers · 2024Article
- Peptide therapeutics in the management of metastatic cancers.RSC advances · 2022Review
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- PAR2 Promoter Hypomethylation Regulates PAR2 Gene Expression and Promotes Lung Adenocarcinoma Cell Progression.Computational and mathematical methods in medicine · 2021Article
- Critical Adjuvant Influences on Preventive Anti-Metastasis Vaccine Using a Structural Epitope Derived from Membrane Type Protease PRSS14.Immune network · 2020Article
- A JUN N-terminal kinase inhibitor induces ectodomain shedding of the cancer-associated membrane protease Prss14/epithin via protein kinase CβII.The Journal of biological chemistry · 2020Article
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule.
methodsThe study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis.
resultsPrss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro.
conclusionOur study demonstrates that Prss14/ST14 is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.
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