IgA Fc-folate conjugate activates and recruits neutrophils to directly target triple-negative breast cancer cells
| Autor: | Dana L Schalk, Tracey J Guerin-Edbauer, Manohar Ratnam, Cecilia L. Speyer, David H. Gorski, Lauren E Leakan, Eric D Frontera, Rafa M. Khansa |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Folate Receptor Alpha Cancer Research Neutrophils medicine.medical_treatment Cell Triple Negative Breast Neoplasms Receptors Fc Article Targeted therapy 03 medical and health sciences Folic Acid 0302 clinical medicine Cell Line Tumor medicine Humans Folate Receptor 1 Receptor Triple-negative breast cancer Peroxidase Antibody-dependent cell-mediated cytotoxicity biology Chemistry Antibody-Dependent Cell Cytotoxicity Cancer medicine.disease Immunoglobulin A 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Myeloperoxidase biology.protein Cancer research Female |
| Zdroj: | Breast Cancer Research and Treatment. 172:551-560 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | PURPOSE: According to the American Cancer Society, 1 in 8 women in the U.S. will develop breast cancer, with triple negative breast cancer (TNBC) comprising 15-20% of all breast cancer cases. TNBC is an aggressive subtype due to its high metastatic potential and lack of targeted therapy. Recently, folate receptor alpha (FRA) is found to be expressed on 80% of TNBC with high expression correlating with poor prognosis. In this study, we examined whether binding IgA Fc-folate molecules to FRA receptors on TNBC cells can elicit and induce neutrophils (PMNs), by binding their FcαR1 receptors, to destroy TNBC cells. METHODS: FRA was analyzed on TNBC cells and binding assays were performed using (3)H-folate. Fc-folate was synthesized by linking Fc-fragments of IgA via amine groups to folate. Binding specificity and antibody dependent cellular cytotoxicity (ADCC) potential of Fc-folate to FcαR1 was confirmed by measuring PMN adhesion and myeloperoxidase (MPO) release in a cell-based ELISA. Fc-folate binding to FRA-expressing TNBC cells inducing PMNs to destroy these cells was determined using (51)Cr-release and calcein-labeling assays. RESULTS: Our results demonstrate expression of FRA on TNBC cells at levels consistent with folate binding. Fc-folate binds with high affinity to FRA compared to whole IgA-folate and induces MPO release from PMN when bound to FcαR1. Fc-folate inhibited binding of (3)H-folate to TNBC cells and induced significant cell lysis of TNBC cells when incubated in the presence of PMNs. CONCLUSION: These findings support the hypothesis that an IgA Fc-folate conjugate can destroy TNBC cells by eliciting PMN-mediated ADCC. |
| Databáze: | OpenAIRE |
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