Unraveling Bv8

Researchers at Genentech Inc. have added three big pieces to the puzzle of how prokineticin 2 (PROK2; Bv8), a cytokine secreted by myeloid cells in the bone marrow, regulates tumor-related angiogenesis. The findings, published in Nature, show that expression of Bv8 is upregulated by G-CSF and by tumors, and that anti-Bv8 antibodies have synergy with both anti-VEGF antibodies and chemotherapeutics.

These results suggest that anti-Bv8 antibodies could be combined with other angiogenesis inhibitors to improve cancer therapy, including Genentech's anti-VEGF antibody, Avastin bevacizumab, which is marketed for metastatic colorectal cancer and non-small cell lung cancer.

Napoleone Ferrara, a research fellow in tumor biology and angiogenesis at Genentech and leader of the group that authored the paper in Nature,1 has spent the last several years forming a picture of how noncancerous cells promote and regulate tumor-associated angiogenesis. One theory is that these noncancerous cells are recruited by the tumor cells to locally secrete proteins that either support or accelerate angiogenesis.

As part of this work, in 2004, his group reported that Bv8 and a related protein, prokineticin 1 (PROK1; EG-VEGF), promoted angiogenesis and mobilized cells from bone marrow, although only Bv8 was expressed in the bone marrow.2

Another paper, published by Ferrara's group in mid-2007, identified CD11b+/Gr1+ myeloid cells as key mediators of how somemouse cancer cell lines become refractory to VEGF inhibition.3

The most recent work bridges

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