Cancer research (Chicago, Ill.), 2006-04, Vol.66 (8), p.4349-4356
2006
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Details
- Autor(en) / Beteiligte
- Titel
- Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts
- Ist Teil von
- Cancer research (Chicago, Ill.), 2006-04, Vol.66 (8), p.4349-4356
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2006
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (host) CSF-1 (anti-CSF-1 Fab). Mice bearing human, chemoresistant MCF-7 breast cancer xenografts were treated with combination chemotherapy (CMF: cyclophosphamide, methotrexate, 5-fluorouracil; cycled twice i.p.), anti-CSF-1 Fab (i.p., cycled every 3 days for 14 days), combined CMF and anti-CSF-1 Fab, or with Ringer's solution as a control. Anti-CSF-1 Fab alone suppressed tissue CSF-1 and retarded tumor growth by 40%. Importantly, in combination with CMF, anti-CSF-1 Fab reversed chemoresistance of MCF-7 xenografts, suppressing tumor development by 56%, down-regulating expression of the chemoresistance genes breast cancer-related protein, multidrug resistance gene 1, and glucosylceramide synthase, and prolonging survival significantly. Combined treatment also reduced angiogenesis and macrophage recruitment and down-regulated tumor matrix metalloproteinase-2 (MMP-2) and MMP-12 expression. These studies support the paradigm of CSF-1 blockade in the treatment of solid tumors and show that anti-CSF-1 antibodies are potential therapeutic agents for the treatment of mammary cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.can-05-3523Titel-ID: cdi_proquest_miscellaneous_19442136
- Format
- –
- Schlagworte
- Animals, Antineoplastic agents, Antineoplastic Combined Chemotherapy Protocols - administration & dosage, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Biological and medical sciences, Breast Neoplasms - drug therapy, Breast Neoplasms - enzymology, Breast Neoplasms - immunology, Breast Neoplasms - pathology, Cell Growth Processes - drug effects, Cell Growth Processes - physiology, Cell Line, Tumor, Cyclophosphamide - administration & dosage, DNA Primers, Down-Regulation - drug effects, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Fluorouracil - administration & dosage, Gynecology. Andrology. Obstetrics, Humans, Immunoglobulin Fragments - chemistry, Immunoglobulin Fragments - immunology, Immunoglobulin Fragments - pharmacology, Macrophage Colony-Stimulating Factor - antagonists & inhibitors, Macrophage Colony-Stimulating Factor - biosynthesis, Macrophage Colony-Stimulating Factor - genetics, Macrophage Colony-Stimulating Factor - immunology, Mammary gland diseases, Matrix Metalloproteinases - biosynthesis, Matrix Metalloproteinases - genetics, Medical sciences, Methotrexate - administration & dosage, Mice, Pharmacology. Drug treatments, Receptor, Macrophage Colony-Stimulating Factor - genetics, RNA, Messenger - genetics, Tumors, Vascular Endothelial Growth Factor A - genetics, Vascular Endothelial Growth Factor Receptor-1 - genetics, Vascular Endothelial Growth Factor Receptor-2 - genetics, Xenograft Model Antitumor Assays