Bv8 regulates myeloid-cell-dependent tumour angiogenesis

Farbod Shojaei, Xiumin Wu, Cuiling Zhong, Lanlan Yu, Xiao-Huan Liang, Jenny Yao, Dominique Blanchard, Carlos Bais, Franklin V. Peale, Nicholas van Bruggen, Calvin Ho, Jed Ross, Martha Tan, Richard A. D. Carano, Y. Gloria Meng and Napoleone Ferrara ()
Additional contact information
Farbod Shojaei: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Xiumin Wu: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Cuiling Zhong: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Lanlan Yu: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Xiao-Huan Liang: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Jenny Yao: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Dominique Blanchard: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Carlos Bais: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Franklin V. Peale: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Nicholas van Bruggen: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Calvin Ho: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Jed Ross: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Martha Tan: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Richard A. D. Carano: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Y. Gloria Meng: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Napoleone Ferrara: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA

Nature, 2007, vol. 450, issue 7171, 825-831

Abstract: Abstract 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.

Date: 2007
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DOI: 10.1038/nature06348

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