Targeting Platelet-Derived Growth Factor Receptor on Endothelial Cells of Multidrug-Resistant Prostate Cancer
Autor: | Christopher J. Logothetis, Joseph E. Busby, Marva Maya, Toru Nakamura, Sertac Yazici, Isaiah J. Fidler, Junqin He, Kim Anh Do, Xuemei Wang, Sun Jin Kim, Dominic Fan, Hisanori Uehara, Paul Mathew |
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Rok vydání: | 2006 |
Předmět: |
Male
CD31 Cancer Research Platelet-derived growth factor medicine.medical_treatment Fluorescent Antibody Technique Apoptosis Piperazines Mice Random Allocation chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols Tumor Cells Cultured Receptors Platelet-Derived Growth Factor Phosphorylation Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Bone metastasis Protein-Tyrosine Kinases Immunohistochemistry Drug Resistance Multiple Endothelial stem cell Oncology Paclitaxel Lymphatic Metastasis Benzamides Imatinib Mesylate medicine.drug medicine.medical_specialty Blotting Western Mice Nude Antineoplastic Agents Bone Neoplasms Internal medicine In Situ Nick-End Labeling medicine Animals Humans Protein Kinase Inhibitors Chemotherapy Tibia business.industry Microcirculation Endothelial Cells Prostatic Neoplasms Imatinib medicine.disease Antineoplastic Agents Phytogenic Pyrimidines Imatinib mesylate Endocrinology chemistry Drug Resistance Neoplasm Cancer research business Neoplasm Transplantation |
Zdroj: | JNCI: Journal of the National Cancer Institute. 98:783-793 |
ISSN: | 1460-2105 0027-8874 |
Popis: | Background: Inhibiting phosphorylation of platelet-derived growth factor receptor (PDGFR) by treatment with the PDGFR kinase inhibitor imatinib and the chemotherapeutic agent paclitaxel reduces the incidence and size of human prostate cancer bone lesions in nude mice. Because tumor cells and tumor-associated endothelial cells express activated PDGFR, the primary target for imatinib has been unclear. Methods: We selected multidrug-resistant human PC-3MM2 prostate cancer cells (termed PC-3MM2-MDR cells) by culturing them in increasing concentrations of paclitaxel. PC-3MM2-MDR cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group). Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1). All statistical tests were two-sided. Results: PC-3MM2-MDR cells were resistant to paclitaxel and imatinib in vitro. Treatment of implanted mice with imatinib plus paclitaxel led to statistically signifi cant decreases in bone tumor incidence (control = 19 mice with tumors of 19 mice total; imatinib plus paclitaxel = four of 18 mice; P |
Databáze: | OpenAIRE |
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