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

被引：232

作者：

Welford, Abigail F. ^{[1
,2
]}

Biziato, Daniela ^{[3
,4
,5
]}

Coffelt, Seth B. ^{[1
]}

Nucera, Silvia ^{[3
,4
,5
]}

Fisher, Matthew ^{[2
]}

Pucci, Ferdinando ^{[3
,4
,5
]}

Di Serio, Clelia ^{[5
,6
]}

Naldini, Luigi ^{[3
,4
,5
]}

De Palma, Michele ^{[3
,4
]}

Tozer, Gillian M. ^{[2
]}

Lewis, Claire E. ^{[1
]}

机构：

[1] Univ Sheffield, Sch Med, Acad Unit Inflammat & Tumour Targeting, Sheffield S10 2RX, S Yorkshire, England

[2] Univ Sheffield, Sch Med, Tumour Microcirculat Grp, Sheffield S10 2RX, S Yorkshire, England

[3] Ist Sci San Raffaele, Angiogenesis & Tumor Targeting Unit, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy

[4] Ist Sci San Raffaele, HSR TIGET, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy

[5] Univ Vita Salute San Raffaele, Milan, Italy

[6] Univ Ctr Stat Biomed Sci CUSSB, Milan, Italy

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2011年 / 121卷 / 05期

基金：

欧洲研究理事会;

关键词：

A-4; PHOSPHATE; MYELOMONOCYTIC CELLS; NORMAL-TISSUES; BONE-MARROW; TUMOR; MONOCYTES; ANGIOGENESIS; RECRUITMENT; BLOOD; VASCULOGENESIS;

D O I：

10.1172/JCI44562

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页码：1969 / 1973

页数：5

共 25 条

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Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells [J].