{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:01:55Z","timestamp":1781103715185,"version":"3.54.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,8]]},"abstract":"<jats:p>\n                    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\u2013VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using\n                    <jats:italic>plgf<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1209310110","type":"journal-article","created":{"date-parts":[[2012,12,24]],"date-time":"2012-12-24T23:14:38Z","timestamp":1356390878000},"page":"654-659","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs"],"prefix":"10.1073","volume":"110","author":[{"given":"Eva-Maria Eleonora","family":"Hedlund","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masabumi","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weide","family":"Zhong","sequence":"additional","affiliation":[{"name":"First Municipal People's Hospital, Guangzhou Medical University, Guangzhou 510180, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University, Tianjin 300070, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Hosaka","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihai","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;"},{"name":"Department of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,12,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"crossref","unstructured":"Y Cao et al. 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