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Updated: Aug 31, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
A novel ADC targeting cell surface fibromodulin in a mouse model of triple-negative breast cancer
Mozhan Haji Ghaffari1, Miganoosh Simonian2, Ali Salimi2
1Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background:
Triple-negative breast cancers (TNBCs) are highly aggressive and metastatic. To date, finding efficacious targeted therapy molecules might be the only window of hope to cure cancer. Fibromodulin (FMOD), is ectopically highly expressed on the surface of Chronic Lymphocytic Leukemia (CLL) and bladder carcinoma cells; thus, it could be a promising molecule for targeted therapy of cancer. The objective of this study was to evaluate cell surface expression of FMOD in two TNBC cell lines and develop an antibody-drug conjugate (ADC) to target FMOD positive TNBC in vitro and in vivo.
Materials And Methods:
Two TNBC-derived cell lines 4T1 and MDA-MB-231 were used in this study. The specific binding of anti-FMOD monoclonal antibody (mAb) was evaluated by flow cytometry and its internalization was verified using phAb amine reactive dye. A microtubulin inhibitor Mertansine (DM1) was used for conjugation to anti-FMOD mAb. The binding efficacy of FMOD-ADC was assessed by immunocytochemistry technique. The anti-FMOD mAb and FMOD-ADC apoptosis induction were measured using Annexin V-FITC and flow cytometry. Tumor growth inhibition of anti-FMOD mAb and FMOD-ADC was evaluated using BALB/c mice injected with 4T1 cells.
Results:
Our results indicate that both anti-FMOD mAb and FMOD-ADC recognize cell surface FMOD molecules. FMOD-ADC could induce apoptosis in 4T1 and MDA-MB-231 cells in vitro. In vivo tumor growth inhibition was observed using FMOD-ADC in 4T1 inoculated BALB/c mice.
Conclusion:
Our results suggests high cell surface FMOD expression could be a novel bio-marker TNBCs. Furthermore, FMOD-ADC could be a promising candidate for targeting TNBCs.
Insights
Fibromodulin (FMOD) is a potential target for aggressive triple-negative breast cancers (TNBCs). An antibody-drug conjugate (ADC) targeting FMOD showed promising results in vitro and in vivo, suggesting it could be a novel therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Triple-negative breast cancers (TNBCs) are aggressive and metastatic, necessitating novel targeted therapies.
- Fibromodulin (FMOD) is aberrantly expressed on cancer cells, presenting a potential therapeutic target.
- This study investigated FMOD as a target for TNBC therapy.
Purpose of the Study:
- To evaluate cell surface FMOD expression in TNBC cell lines.
- To develop an antibody-drug conjugate (ADC) targeting FMOD.
- To assess the efficacy of the FMOD-ADC in vitro and in vivo.
Main Methods:
- Utilized 4T1 and MDA-MB-231 TNBC cell lines.
- Developed an anti-FMOD monoclonal antibody (mAb) conjugated to Mertansine (DM1) to create FMOD-ADC.
- Assessed binding, internalization, and apoptosis induction via flow cytometry and immunocytochemistry.
- Evaluated in vivo tumor growth inhibition in a murine model.
Main Results:
- Confirmed cell surface FMOD expression and recognition by anti-FMOD mAb and FMOD-ADC.
- Demonstrated FMOD-ADC-induced apoptosis in TNBC cell lines in vitro.
- Observed significant tumor growth inhibition by FMOD-ADC in vivo.
Conclusions:
- High cell surface FMOD expression is a potential novel biomarker for TNBCs.
- FMOD-ADC demonstrates promise as a targeted therapy for TNBCs.
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