Postsurgical Adjuvant Tumor Therapy by Combining Anti-Angiopoietin-2 and Metronomic Chemotherapy Limits Metastatic Growth

被引：144

作者：

Srivastava, Kshitij ^{[1
]}

Hu, Junhao ^{[1
]}

Korn, Claudia ^{[1
]}

Savant, Soniya ^{[1
,2
]}

Teichert, Martin ^{[1
,2
]}

Kapel, Stephanie S. ^{[1
]}

Jugold, Manfred ^{[3
]}

Besemfelder, Eva ^{[1
]}

Thomas, Markus ^{[4
]}

Pasparakis, Manolis ^{[5
,6
]}

Augustin, Hellmut G. ^{[1
,2
,7
]}

机构：

[1] German Canc Res Ctr Heidelberg DKFZ ZMBH Alliance, Div Vasc Oncol & Metastasis, D-69121 Heidelberg, Germany

[2] Heidelberg Univ, Med Fac Mannheim, Dept Vasc Biol & Tumor Angiogenesis CBTM, D-68167 Mannheim, Germany

[3] German Canc Res Ctr, Small Anim Imaging Ctr, Heidelberg, Germany

[4] GmbH, Roche Diagnost, D-82377 Penzberg, Germany

[5] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50923 Cologne, Germany

[6] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50923 Cologne, Germany

[7] German Canc Consortium, D-69120 Heidelberg, Germany

来源：

CANCER CELL | 2014年 / 26卷 / 06期

关键词：

BEVACIZUMAB-CONTAINING THERAPY; BREAST-CANCER; MYELOID CELLS; ANTIANGIOGENIC THERAPY; COLORECTAL-CANCER; VEGF-A; ANGIOGENESIS; ANGIOPOIETIN-2; TRIAL; EXPRESSION;

D O I：

10.1016/j.ccell.2014.11.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Antiangiogenic tumor therapy has failed in the adjuvant setting. Here we show that inhibition of the Tie2 ligand angiopoietin-2 (Ang2) effectively blocks metastatic growth in preclinical mouse models of postsurgical adjuvant therapy. Ang2 antibody treatment combines well with low-dose metronomic chemotherapy (LDMC) in settings in which maximum-dose chemotherapy does not prove effective. Mechanistically, Ang2 blockade could be linked to quenching the inflammatory and angiogenic response of endothelial cells (ECs) in the metastatic niche. Reduced EC adhesion molecule and chemokine expression inhibits the recruitment of tumor-promoting CCR2(+)Tie2(-) metastasis-associated macrophages. Moreover, LDMC contributes to therapeutic efficacy by inhibiting the recruitment of protumorigenic bone marrow-derived myeloid cells. Collectively, these data provide a rationale for mechanism-guided adjuvant tumor therapies.

引用

收藏

页码：880 / 895

页数：16

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