A New Angiogenesis Weapon

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Science  16 Nov 2007:
Vol. 318, Issue 5853, pp. 1041
DOI: 10.1126/science.318.5853.1041c

Tumors need blood, and they secrete angiogenic molecules such as vascular endothelial growth factor (VEGF) to encourage new blood vessels to form. Although an antibody directed against VEGF (αVEGF) can prolong life when given in conjunction with chemotherapy to individuals with certain cancers, inhibiting VEGF signaling can elicit adverse side effects and switch on alternative angiogenic mechanisms in tumor cells. Noting that placental growth factor (PlGF, a VEGF family member) is not required for normal development of the vasculature but has been implicated in pathological angiogenesis, Fischer et al. investigated the effect on tumors of an antibody directed against PlGF (αPlGF). In a mouse model, αPIGF by itself inhibited the growth or metastasis of melanoma and of colon and pancreatic carcinomas, and enhanced inhibition of tumor growth by the chemotherapeutic agents gemcitabine and cyclophosphamide, as well as the anticancer effects of an antibody directed against the VEGF receptor (αVEGFR). The processes inhibited included tumor angiogenesis and lymphangiogenesis, as well as the recruitment of proangiogenic macrophages. On the other hand, αPlGF did not turn on the expression of proangiogenic genes, nor did it mimic or enhance αVEGFR-dependent side effects; indeed, pregnant mice treated with αPlGF delivered litters of healthy pups. Thus, the authors hope that αPlGF might represent a useful addition to the anticancer armamentarium. — EMA

Cell 131, 463 (2007).

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