Bv8 regulates myeloid-cell-dependent tumour angiogenesis

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Bone marrow-derived cells are crucial for tumor angiogenesis, but mechanisms remain unclear.
• Prokineticins, including Bv8 (prokineticin 2), regulate angiogenesis and hematopoietic cell mobilization.
• Bv8 is expressed in bone marrow, suggesting a role in tumor-associated myeloid cell mobilization.

Purpose of the Study:

• To elucidate the role of Bv8 in tumor angiogenesis and myeloid cell mobilization.
• To investigate the regulation of Bv8 expression in myeloid cells.
• To evaluate the therapeutic potential of anti-Bv8 antibodies in cancer models.

Main Methods:

• Tumor implantation in mice to study Bv8 expression in myeloid cells (CD11b+Gr1+).
• Identification of granulocyte colony-stimulating factor as a regulator of Bv8.
• Administration of anti-Bv8 antibodies and adenoviral Bv8 delivery in vivo.
• Assessment of tumor growth, angiogenesis, and myeloid cell populations.

Main Results:

• Tumor cell implantation upregulated Bv8 in myeloid cells, regulated by granulocyte colony-stimulating factor.
• Anti-Bv8 antibodies inhibited myeloid cell mobilization and tumor angiogenesis.
• Adenoviral Bv8 delivery promoted angiogenesis within tumors.
• Anti-Bv8 treatment suppressed tumor growth, angiogenesis, and myeloid cell infiltration, with additive effects to anti-VEGF or chemotherapy.

Conclusions:

• Bv8 plays a dual role in cancer by modulating myeloid cell mobilization from bone marrow and promoting local tumor angiogenesis.
• Targeting Bv8 represents a promising therapeutic strategy for inhibiting tumor growth and angiogenesis.