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2. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

Author

Welford, Abigail F., Biziato, Daniela, Coffelt, Seth B., Nucera, Silvia, Fisher, Matthew, Pucci, Ferdinando, Di Serio, Clelia, Naldini, Luigi, De Palma, Michele, Tozer, Gillian M., and Lewis, Claire E.

Subjects
Tumors -- Research -- Drug therapy, Angiogenesis inhibitors -- Health aspects -- Research, Macrophages -- Physiological aspects -- Research -- Health aspects, Health care industry
Abstract

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we [...]

Published
2011
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6. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

Author

Abigail F. Welford, Michele De Palma, Seth B. Coffelt, Luigi Naldini, Silvia Nucera, Gillian M. Tozer, Ferdinando Pucci, Matthew Fisher, Claire E. Lewis, Daniela Biziato, Clelia Di Serio, Welford, A. F., Biziato, D., Coffelt, S. B., Nucera, S., Fisher, M., Pucci, F., DI SERIO, Mariaclelia, Naldini, L., De Palma, M., Tozer, G. M., and Lewis, C. E.

Subjects
Receptors, CXCR4, Chemokine, Pathology, medicine.medical_specialty, Transgene, Mammary Neoplasms, Animal, Mice, Transgenic, Cell Separation, CXCR4, Flow cytometry, Mice, Necrosis, 03 medical and health sciences, 0302 clinical medicine, Stilbenes, medicine, Animals, Receptor, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, biology, Brief Report, Macrophages, Receptor Protein-Tyrosine Kinases, General Medicine, Hypoxia (medical), Flow Cytometry, Antineoplastic Agents, Phytogenic, Receptor, TIE-2, Angiopoietin receptor, Chemokine CXCL12, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Tumor necrosis factor alpha, medicine.symptom, Neoplasm Transplantation
Abstract

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies.

Published
2011
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