Open AccessENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours
Author(s) -
Gromova Petra,
Rubin Brian P.,
Thys An,
Cullus Pierre,
Erneux Christophe,
Vanderwinden JeanMarie
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01315.x
Subject(s) - biology , endoglin , gist , pdgfra , stromal cell , microbiology and biotechnology , interstitial cell of cajal , demethylating agent , cd34 , proto oncogene proteins c kit , cancer research , imatinib mesylate , immunohistochemistry , imatinib , stem cell factor , dna methylation , gene expression , immunology , haematopoiesis , gene , stem cell , genetics , myeloid leukemia
ENDOGLIN/CD105 (ENG) is a transmembrane glycoprotein and an auxiliary unit of the transforming growth factor‐β (TGF‐β); receptor, expressed predominantly in vascular endothelium. Noteworthy, Eng mRNA expression has been reported also in Kit + interstitial cells of Cajal (ICC) in the mouse intestine. Gastrointestinal stromal tumours (GIST) are thought to derive from ICC. Here we have investigated Eng expression in the Kit K641E mouse GIST model, in human GIST and in the Ba/F3 cell model. In wild type (WT) mouse antrum, Eng immunoreactivity (‐ir) was detected in CD34 + /CD31 + endothelium and in Kit + ICC. In Kit K641E mice, hyperplasia of Kit + cells made Eng‐ir even more evident. Quantitative PCR confirmed the increased expression of Eng transcript in Kit K641E mice. On human GIST TMA, 26/49 cases stained positive for ENG. Strong ENG staining was associated with malignant and high‐risk tumours. ENG negative cases were predominantly of the epithelioid type or harboured PDGFRA mutation. In vitro , Eng mRNA was up‐regulated in Ba/F3 cell lines stably expressing various oncogenic Kit mutations (K641E, del559, del814). This effect appeared to be independent of Kit activation, as neither the stimulation of WT Kit by its ligand SCF, nor the inhibition of Kit autophosphorylation by imatinib mesylate in oncogenic mutants, altered Eng expression. Elevated Eng expression in Kit oncogenic mutants appeared rather to be indirectly mediated by DNA hypomethylation, because treatment with the demethylating agent 5‐Aza/dC increased Eng mRNA expression in Kit WT cells. ENG expression in ICC and in GIST deserves further consideration as ENG is emerging as a potential target for cancer therapy.