title: VEGFR-1 expression levels predict occurrence of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma.
abstract: Blocking angiogenesis by inhibiting VEGF represents an established therapeutic strategy in many cancers. The role of placental growth factor (PlGF) and of its receptor VEGFR-1 in tumor biology remain more elusive. Currently, humanized monoclonal antibodies against PlGF are studied in early phase clinical trials because PlGF inhibition blocked murine tumor growth and angiogenesis. In contrast to mice exclusively expressing one PlGF isoform (PlGF-2), humans can produce four PlGF isoforms (PlGF1-4). Surprisingly nothing is yet known about expression of all four PlGF isoforms in human cancer, because until now mostly total PlGF levels or PlGF-1/2 were analyzed without discriminating further. In this study we determined mRNA expression levels of PlGF1-4 and of VEGFR-1 by QRT-PCR in human esophageal tumor tissue and investigated whether gene expression levels correlate with clinical data. PlGF-1 and -2 were expressed in virtually all analyzable tumors, whereas PlGF-3 and -4 were present in tumors of 59 and 74 % of patients, respectively. MRNA Expression levels of all four splice variants correlated with each other. In contrast, PlGF-1 and -2 mRNA expression was lower in esophageal control tissue and PlGF-3 and -4 mRNA were  undetectable. VEGFR-1 was expressed by more than 80 % of patients. Interestingly, VEGFR-1 expression levels significantly correlate with presence of disseminated tumor cells (DTCs) in bone marrow. Patients with DTCs exhibit lower VEGFR-1 mRNA expression than patients without DTCs. Pending validation in other types of cancer, expression levels of VEGFR-1 might be useful as surrogate marker for DTCs.
authors.affiliation: Department of Hematology and Oncology with Sections BMT and Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schultze
authors.forename: Isabel
authors.initials: I
authors.lastname: Ben Batalla
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Michael
authors.initials: M
authors.lastname: Bubenheim
authors.forename: Emre
authors.initials: E
authors.lastname: Yekebas
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Effenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Sonja
authors.initials: S
authors.lastname: Loges
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology; D001483:Base Sequence; D001853:Bone Marrow; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1