A New Angiogenesis Inhibitor

Abstract

Although antibodies directed against vascular endothelial growth factor (αVEGF) can prolong life when given to individuals with certain cancers in conjunction with chemotherapy, inhibition of VEGF signaling can elicit adverse effects and also stimulate the production of alternative angiogenic mechanisms in tumors (see Jain and Xu). Noting that placental growth factor [PIGF, a member of the VEGF family that binds VEGF receptor 1 (VEGFR-1)] is not required for normal development and maintenance of the vasculature but has been implicated in pathological angiogenesis, Fischer et al . investigated the effect on tumors of an antibody directed against PIGF (αPIGF). αPIGF inhibited the growth or metastasis or both of various tumors in mice, some of which were resistant to inhibition of VEGFR signaling. Furthermore, αPIGF enhanced inhibition of tumor growth by the chemotherapeutic agents gemcitabine and cyclophosphamide, as well as the anticancer effects of an antibody directed against VEGFR-2 (αVEGFR-2). αPIGF inhibited tumor angiogenesis and lymphangiogenesis, as well as tumor recruitment of proangiogenic macrophages. αPIGF failed to increase the expression of several proangiogenic genes stimulated by αVEGFR-2, and it neither mimicked nor enhanced αVEGFR-2-dependent side effects. Indeed, pregnant mice treated with αPIGF delivered litters of healthy pups. Thus, the authors hope that αPIGF might represent a useful addition to the current anticancer armamentarium. C. Fischer, B. Jonckx, M. Mazzone, S. Zacchigna, S. Loges, L. Pattarini, E. Chorianopoulos, L. Liesenborghs, M. Koch, M. De Mol, M. Autiero, S. Wyns, S. Plaisance, L. Moons, N. van Rooijen, M. Giacca, J.-M. Stassen, M. Dewerchin, D. Collen, P. Carmeliet, Anti-PIGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131 , 463-475 (2007). [PubMed] R. K. Jain, L. Xu, αPlGF: A new kid on the antiangiogenesis block. Cell 131 , 443-445 (2007). [PubMed]