Keratoepithelin reverts the suppression of tissue factor pathway inhibitor 2 by MYCN in human neuroblastoma: a mechanism to inhibit invasion.
Neuroblastoma is the most frequent solid malignancy of children. The most reliable prognostic factor in neuroblastoma is the amplification status of the MYCN oncogene, but exceptions from this rule have been observed. Recently we have demonstrated that keratoepithelin (BIGH3, TGFBI) expression significantly reduces proliferation and invasion of neuroblastomas in vitro and in vivo. In these experiments, we also observed that tissue factor pathway inhibitor 2 (TFPI2, PP5, MSPI), a potent inhibitor of matrix-metalloproteinases, is most prominently up-regulated. As MYCN-amplified neuroblastomas are highly invasive, we sought to determine the interaction between MYCN, keratoepithelin and TFPI2. In this study we provide initial evidence that i) keratoepithelin expression in neuroblastoma inversely correlates with MYCN expression; ii) TFPI2 expression in neuroblastoma also correlates inversely with MYCN expression but positively with keratoepithelin expression and iii) keratoepithelin induces elevated TFPI2 transcript levels in neuroblastoma cells without alterations of MYCN expression.
Becker
Juergen
J
Zentrum Anatomie, Abteilung Anatomie und Zellbiologie, Universitätsmedizin Göttingen, D-37075 Göttingen, Germany. juergen.becker@med.uni-goettingen.de
Volland
Sonja
S
Noskova
Ievgeniia
I
Schramm
Alexander
A
Schweigerer
Lothar L
LL
Wilting
Joerg
J
D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005784:Gene Amplification; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C459801:MYCN protein, human; C021240:tissue-factor-pathway inhibitor 2