VEGFR-1 expression levels predict occurrence of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma
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VEGFR-1 expression levels predict occurrence of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma. / Schultze, Alexander; Ben-Batalla, Isabella; Riethdorf, Sabine; Bubenheim, Michael; Yekebas, Emre F.; Erbersdobler, Andreas; Reichelt, Uta; Harms-Effenberger, Katharina; Schmidt, Thomas; Izbicki, Jakob R.; Bokemeyer, Carsten; Pantel, Klaus; Fiedler, Walter; Loges, Sonja.
in: CLIN EXP METASTAS, Jahrgang 29, Nr. 8, 8, 12.2012, S. 879-887.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - VEGFR-1 expression levels predict occurrence of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma
AU - Schultze, Alexander
AU - Ben-Batalla, Isabella
AU - Riethdorf, Sabine
AU - Bubenheim, Michael
AU - Yekebas, Emre F.
AU - Erbersdobler, Andreas
AU - Reichelt, Uta
AU - Harms-Effenberger, Katharina
AU - Schmidt, Thomas
AU - Izbicki, Jakob R.
AU - Bokemeyer, Carsten
AU - Pantel, Klaus
AU - Fiedler, Walter
AU - Loges, Sonja
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Molecular Sequence Data
KW - Base Sequence
KW - RNA, Messenger/genetics/metabolism
KW - Protein Isoforms/genetics/metabolism
KW - Neovascularization, Pathologic
KW - Antibodies, Monoclonal, Humanized/immunology
KW - Bone Marrow
KW - Bone Marrow Neoplasms/secondary
KW - Esophageal Neoplasms/genetics/metabolism
KW - Pregnancy Proteins/genetics/immunology/metabolism
KW - Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Molecular Sequence Data
KW - Base Sequence
KW - RNA, Messenger/genetics/metabolism
KW - Protein Isoforms/genetics/metabolism
KW - Neovascularization, Pathologic
KW - Antibodies, Monoclonal, Humanized/immunology
KW - Bone Marrow
KW - Bone Marrow Neoplasms/secondary
KW - Esophageal Neoplasms/genetics/metabolism
KW - Pregnancy Proteins/genetics/immunology/metabolism
KW - Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism
U2 - 10.1007/s10585-012-9477-1
DO - 10.1007/s10585-012-9477-1
M3 - SCORING: Journal article
C2 - 22484977
VL - 29
SP - 879
EP - 887
JO - CLIN EXP METASTAS
JF - CLIN EXP METASTAS
SN - 0262-0898
IS - 8
M1 - 8
ER -
