Bv8 regulates myeloid-cell-dependent tumour angiogenesis

被引：525

作者：

Shojaei, Farbod ^{[1
]}

Wu, Xiumin ^{[1
]}

Zhong, Cuiling ^{[1
]}

Yu, Lanlan ^{[1
]}

Liang, Xiao-Huan ^{[1
]}

Yao, Jenny ^{[1
]}

Blanchard, Dominique ^{[1
]}

Bais, Carlos ^{[1
]}

Peale, Franklin V. ^{[1
]}

van Bruggen, Nicholas ^{[1
]}

Ho, Calvin ^{[1
]}

Ross, Jed ^{[1
]}

Tan, Martha ^{[1
]}

Carano, Richard A. D. ^{[1
]}

Meng, Y. Gloria ^{[1
]}

Ferrara, Napoleone ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

来源：

NATURE | 2007年 / 450卷 / 7171期

关键词：

D O I：

10.1038/nature06348

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Bone- marrow- derived cells facilitate tumour angiogenesis, but the molecular mechanisms of this facilitation are incompletely understood. We have previously shown that the related EG- VEGF and Bv8 proteins, also known as prokineticin 1 ( Prok1) and prokineticin 2 ( Prok2), promote both tissue- specific angiogenesis and haematopoietic cell mobilization. Unlike EG- VEGF, Bv8 is expressed in the bone marrow. Here we show that implantation of tumour cells in mice resulted in upregulation of Bv8 in CD11b(+) Gr1(+) myeloid cells. We identified granulocyte colony- stimulating factor as a major positive regulator of Bv8 expression. Anti- Bv8 antibodies reduced CD11b(+) Gr1(+) cell mobilization elicited by granulocyte colony- stimulating factor. Adenoviral delivery of Bv8 into tumours was shown to promote angiogenesis. Anti- Bv8 antibodies inhibited growth of several tumours in mice and suppressed angiogenesis. Anti- Bv8 treatment also reduced CD11b(+) Gr1(+) cells, both in peripheral blood and in tumours. The effects of anti- Bv8 antibodies were additive to those of anti- Vegf antibodies or cytotoxic chemotherapy. Thus, Bv8 modulates mobilization of CD11b(+) Gr1(+) cells from the bone marrow during tumour development and also promotes angiogenesis locally.

引用

页码：825 / U6

页数：10

共 45 条

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