NGR-TNF, a novel vascular-targeting agent, does not induce cytokine recruitment of proangiogenic bone marrow-derived cells.
Br J Cancer
; 109(2): 360-9, 2013 Jul 23.
Article
en En
| MEDLINE
| ID: mdl-23828516
ABSTRACT
BACKGROUND:
Administration of certain chemotherapy drugs at the maximum tolerated dose, vascular-disrupting agents (VDAs) and irradiation can induce mobilisation and tumour homing of proangiogenic bone marrow-derived cells (BMDCs). Increases in cytokines and chemokines contribute to such mobilisation that eventually promotes tumour (re)growth. NGR-TNF is a vascular-targeting agent in advanced clinical development, coupling the CNGRCG angiogenic vessel-homing peptide with tumour necrosis factor-alpha (TNF). We investigated whether NGR-TNF mobilises host BMDCs and growth factors.METHODS:
Blood was obtained from Lewis lung carcinoma and 4T1 tumour-bearing mice at different time points following NGR-TNF, VDA or anti-VEGFR2/flk-1 antibody treatment. Levels of circulating growth factors were assessed by ELISAs. BMDCs were characterised by FACS. Circulating endothelial progenitor cells were defined as CD45(-)/CD13(+)/flk-1(+)/CD117(+)/7AAD(-), Tie2-expressing monocytes as CD45(+)/CD11b(+)/Tie2(+) and myeloid-derived suppressor cells as CD45(+)/CD11b(+)/Gr1(+) cells.RESULTS:
NGR-TNF decreases tumour blood vessel density-inducing apoptosis of tumour and tumour endothelial cells. Unlike VDAs, or high-dose NGR-TNF, lower doses of NGR-TNF, comparable to those used in clinical trials, neither mobilise nor recruit to the tumour site proangiogenic BMDCs or induce host growth factors.CONCLUSION:
Low-dose NGR-TNF exerts antitumour activity without inducing proangiogenic host responses, conceivably important for preventing/overcoming resistance and designing combination therapeutic strategies.
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Bases de datos:
MEDLINE
Asunto principal:
Células de la Médula Ósea
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Quimiotaxis
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Citocinas
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Factor de Necrosis Tumoral alfa
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Inhibidores de la Angiogénesis
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Terapia Molecular Dirigida
Límite:
Animals
Idioma:
En
Revista:
Br J Cancer
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia