Cancer cell, 2013-02, Vol.23 (2), p.249-262
- Germano, Giovanni
- Frapolli, Roberta
- Belgiovine, Cristina
- Anselmo, Achille
- Pesce, Samantha
- Liguori, Manuela
- Erba, Eugenio
- Uboldi, Sarah
- Zucchetti, Massimo
- Pasqualini, Fabio
- Nebuloni, Manuela
- van Rooijen, Nico
- Mortarini, Roberta
- Beltrame, Luca
- Marchini, Sergio
- Fuso Nerini, Ilaria
- Sanfilippo, Roberta
- Casali, Paolo G.
- Pilotti, Silvana
- Galmarini, Carlos M.
- Anichini, Andrea
- Mantovani, Alberto
- D’Incalci, Maurizio
- Allavena, Paola
2013
Details
- Autor(en) / Beteiligte
- Germano, Giovanni
- Frapolli, Roberta
- Belgiovine, Cristina
- Anselmo, Achille
- Pesce, Samantha
- Liguori, Manuela
- Erba, Eugenio
- Uboldi, Sarah
- Zucchetti, Massimo
- Pasqualini, Fabio
- Nebuloni, Manuela
- van Rooijen, Nico
- Mortarini, Roberta
- Beltrame, Luca
- Marchini, Sergio
- Fuso Nerini, Ilaria
- Sanfilippo, Roberta
- Casali, Paolo G.
- Pilotti, Silvana
- Galmarini, Carlos M.
- Anichini, Andrea
- Mantovani, Alberto
- D’Incalci, Maurizio
- Allavena, Paola
- Titel
- Role of Macrophage Targeting in the Antitumor Activity of Trabectedin
- Ist Teil von
- Cancer cell, 2013-02, Vol.23 (2), p.249-262
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- There is widespread interest in macrophages as a therapeutic target in cancer. Here, we demonstrate that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes. In four mouse tumor models, trabectedin caused selective depletion of monocytes/macrophages in blood, spleens, and tumors, with an associated reduction of angiogenesis. By using trabectedin-resistant tumor cells and myeloid cell transfer or depletion experiments, we demonstrate that cytotoxicity on mononuclear phagocytes is a key component of its antitumor activity. Monocyte depletion, including tumor-associated macrophages, was observed in treated tumor patients. Trabectedin activates caspase-8-dependent apoptosis; selectivity for monocytes versus neutrophils and lymphocytes is due to differential expression of signaling and decoy TRAIL receptors. This unexpected property may be exploited in different therapeutic strategies. [Display omitted] ► Trabectedin is a recently approved antitumor agent of marine origin ► Trabectedin activates caspase-8-dependent apoptosis exclusively in myelomonocytes ► In vivo trabectedin reduces monocytes and TAM, and related angiogenesis ► Depletion of TAM is a key component of the antitumor efficacy of trabectedin
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108eISSN: 1878-3686DOI: 10.1016/j.ccr.2013.01.008Titel-ID: cdi_proquest_miscellaneous_1288315039
- Format
- –
- Schlagworte
- Animals, Antineoplastic Agents, Alkylating - therapeutic use, Apoptosis - drug effects, Blotting, Western, Carcinoma, Lewis Lung - drug therapy, Carcinoma, Lewis Lung - metabolism, Carcinoma, Lewis Lung - pathology, Caspase 8 - metabolism, Cell Proliferation, Dioxoles - therapeutic use, Female, Fibrosarcoma - drug therapy, Fibrosarcoma - metabolism, Fibrosarcoma - pathology, Flow Cytometry, Humans, Immunoenzyme Techniques, Macrophages - drug effects, Macrophages - metabolism, Macrophages - pathology, Mice, Monocytes - drug effects, Monocytes - metabolism, Monocytes - pathology, Myeloid Cells - drug effects, Myeloid Cells - metabolism, Myeloid Cells - pathology, Neovascularization, Pathologic - prevention & control, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Phagocytes - drug effects, Phagocytes - metabolism, Phagocytes - pathology, Signal Transduction - drug effects, Tetrahydroisoquinolines - therapeutic use, Tumor Cells, Cultured