title: Human choriocarcinomas: placental growth factor-dependent preclinical tumor models.
abstract: Choriocarcinomas are a rare form of cancer that develops in the uterus from             tissue which would normally become the placenta. Choriocarcinomas are a trophoblastic             gestational disease and have been studied largely to investigate conditions related             to pregnancy such as preeclampsia. Choriocarcinomas are highly angiogenic and             produce high levels of placental growth factor (PlGF) to promote the development             of blood vessels. Upregulation of PlGF expression also occurs during the development             of other human malignancies such as breast cancer and melanoma. Both tumor specimens             and plasma samples have higher levels of PlGF than normal tissues. Hence, PlGF             has emerged as a valid target for anti-angiogenic therapy. The cell lines BeWo,             JAR and JEG-3, derived from human choriocarcinomas, were investigated in vitro             and in vivo for suitability as PlGF-dependent models. BeWo, JAR and JEG-3 cells             were characterized in culture and were implanted into immunodeficient mice to             generate subcutaneous tumors. The PlGF and VEGF angiogenic profiles of the choriocarcinoma             cells and tumors were investigated by ELISA and by immunohistochemical methods.             Double immunofluorescence methods were applied to choriocarcinoma xenograft sections             to characterize the cellular components of the blood vessels. sFLT01, a fusion             protein that neutralizes PlGF, was assessed in cell culture experiments and xenograft             studies. The novel results presented here validate the importance of human choriocarcinoma             cell lines and xenografts in further exploring the role of PlGF in tumor angiogenesis,             for evaluating PlGF as an anti-angiogenic target, and for developing therapies             that may provide clinical benefit.
authors.affiliation: Genzyme Corporation, 49 New York Ave., Framingham, MA 01701-9322, USA. rebecca.bagley@genzyme.com
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Bagley
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Leslie
authors.initials: L
authors.lastname: Kurtzberg
authors.forename: William
authors.initials: W
authors.lastname: Weber
authors.forename: Dinesh
authors.initials: D
authors.lastname: Bangari
authors.forename: William
authors.initials: W
authors.lastname: Brondyk
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D047368:Tumor Burden; D014594:Uterine Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C571127:sFLT01 fusion protein; D000072483:Placenta Growth Factor