| Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs. | |
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MedLine Citation:
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PMID: 23267058 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Eva-Maria Eleonora Hedlund; Xiaojuan Yang; Yin Zhang; Yunlong Yang; Masabumi Shibuya; Weide Zhong; Baocun Sun; Yizhi Liu; Kayoko Hosaka; Yihai Cao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-12-24 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 110 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-09 Completed Date: 2013-03-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 654-9 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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metabolism* Animals Antibodies, Blocking / pharmacology Antineoplastic Agents / metabolism* Cell Line, Tumor Choriocarcinoma / genetics*, metabolism DNA Primers / genetics Drug Resistance, Neoplasm / drug effects Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Humans Male Mice Mice, Inbred C57BL Neovascularization, Pathologic / chemically induced*, metabolism Pregnancy Proteins / metabolism, pharmacology* RNA, Small Interfering / genetics, pharmacology Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A / antagonists & inhibitors* Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Antibodies, Blocking; 0/Antineoplastic Agents; 0/DNA Primers; 0/Pregnancy Proteins; 0/RNA, Small Interfering; 0/Vascular Endothelial Growth Factor A; 144589-93-5/placenta growth factor; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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