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Updated: Jul 8, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Transferrin receptor in primary and metastatic breast cancer: Evaluation of expression and experimental modulation to
Francesca Fontana1, Alison K Esser1, Christopher Egbulefu2
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States of America.
Background:
Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.
Methods:
Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were stained with the FDA-approved MRQ-48 antibody against TfR and graded by staining intensity (H-score). Patient-derived xenografts (PDX) and isogenic metastatic mouse models were used to study in vivo TfR expression and uptake of transferrin.
Results:
TFRC gene and protein expression were high in breast cancer of all subtypes and stages, and in 60-85% of bone metastases. TfR was detectable after neoadjuvant chemotherapy, albeit with some variability. Fluorophore-conjugated transferrin iron chelator deferoxamine (DFO) enhanced TfR uptake in human breast cancer cells in vitro and proved transferrin localization at metastatic sites and correlation of tumor burden relative to untreated tumor mice.
Conclusions:
TfR is expressed in breast cancer, primary, metastatic, and after neoadjuvant chemotherapy. Variability in expression of TfR suggests that evaluation of the expression of TfR in individual patients could identify the best candidates for targeting. Further, systemic iron chelation with DFO may upregulate receptor expression and improve uptake of therapeutics or tracers that use transferrin as a homing ligand.
Insights
Transferrin receptor (TfR) is highly expressed in breast cancer, including metastases and after chemotherapy. Evaluating individual TfR expression can optimize targeted therapies for breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biomedical Imaging
Background:
- Transferrin (Tf) conjugation to nanotherapeutics offers targeted breast cancer treatment.
- Targeting efficacy relies on transferrin receptor (TfR) overexpression.
- TfR expression in primary, metastatic, and relapsed breast cancer requires comprehensive evaluation.
Purpose of the Study:
- To survey TfR expression in diverse breast cancer samples.
- To investigate TfR modulation in experimental breast cancer models.
- To assess TfR as a target for breast cancer therapies.
Main Methods:
- Analysis of twelve public gene expression datasets.
- Generation of tissue microarrays (TMAs) for matched primary and metastatic tumors.
- Immunohistochemical staining of TMAs using an FDA-approved anti-TfR antibody (MRQ-48).
- In vivo studies using patient-derived xenografts (PDX) and isogenic mouse models.
Main Results:
- High TFRC gene and protein expression observed across all breast cancer subtypes and stages.
- TfR detected in 60-85% of bone metastases and post-neoadjuvant chemotherapy samples.
- Deferoxamine (DFO) enhanced TfR-mediated uptake in vitro and in vivo, showing transferrin localization at metastatic sites.
Conclusions:
- TfR is consistently expressed in primary, metastatic, and chemotherapy-treated breast cancer.
- Individual TfR expression assessment is crucial for patient selection in targeted therapies.
- Systemic iron chelation with DFO may enhance TfR-mediated delivery of therapeutics and imaging agents.
