Title |
Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, December 2012
|
DOI | 10.1073/pnas.1209310110 |
Pubmed ID | |
Authors |
Eva-Maria Eleonora Hedlund, Xiaojuan Yang, Yin Zhang, Yunlong Yang, Masabumi Shibuya, Weide Zhong, Baocun Sun, Yizhi Liu, Kayoko Hosaka, Yihai Cao |
Abstract |
The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti-VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 5% |
Sweden | 1 | 2% |
Italy | 1 | 2% |
Switzerland | 1 | 2% |
Unknown | 36 | 88% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 24% |
Researcher | 6 | 15% |
Other | 5 | 12% |
Student > Master | 4 | 10% |
Student > Bachelor | 3 | 7% |
Other | 7 | 17% |
Unknown | 6 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 10 | 24% |
Biochemistry, Genetics and Molecular Biology | 8 | 20% |
Medicine and Dentistry | 6 | 15% |
Immunology and Microbiology | 2 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Other | 6 | 15% |
Unknown | 7 | 17% |