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Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy

2011; National Academy of Sciences; Volume: 108; Issue: 28 Linguagem: Inglês

10.1073/pnas.1109029108

1091-6490

Jenny Yao, Xiumin Wu, Guanglei Zhuang, Ian Kasman, Tobias Vogt, Vernon T. Phan, Masabumi Shibuya, Napoleone Ferrara, Carlos Bais,

Cancer, Hypoxia, and Metabolism

PlGF, one of the ligands for VEGFR-1, has been implicated in tumor angiogenesis. However, more recent studies indicate that genetic or pharmacological inhibition of PlGF signaling does not result in reduction of microvascular density in a variety of tumor models. Here we screened 12 human tumor cell lines and identified 3 that are growth inhibited by anti-PlGF antibodies in vivo. We found that efficacy of anti-PlGF treatment strongly correlates with VEGFR-1 expression in tumor cells, but not with antiangiogenesis. In addition, PlGF induced VEGFR-1 signaling and biological responses in tumor cell lines sensitive to anti-PlGF, but not in refractory tumor cell lines or in endothelial cells. Also, genetic ablation of VEGFR-1 signaling in the host did not affect the efficacy of PlGF blockade. Collectively, these findings suggest that the role of PlGF in tumorigenesis largely consists of promoting autocrine/paracrine growth of tumor cells expressing a functional VEGFR-1 rather than stimulation of angiogenesis.