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ENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours.
J Cell Mol Med. 2012 Feb; 16(2):306-17.JC

Abstract

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.

Authors+Show Affiliations

Laboratory of Neurophysiology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21435173

Citation

Gromova, Petra, et al. "ENDOGLIN/CD105 Is Expressed in KIT Positive Cells in the Gut and in Gastrointestinal Stromal Tumours." Journal of Cellular and Molecular Medicine, vol. 16, no. 2, 2012, pp. 306-17.
Gromova P, Rubin BP, Thys A, et al. ENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours. J Cell Mol Med. 2012;16(2):306-17.
Gromova, P., Rubin, B. P., Thys, A., Cullus, P., Erneux, C., & Vanderwinden, J. M. (2012). ENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours. Journal of Cellular and Molecular Medicine, 16(2), 306-17. https://doi.org/10.1111/j.1582-4934.2011.01315.x
Gromova P, et al. ENDOGLIN/CD105 Is Expressed in KIT Positive Cells in the Gut and in Gastrointestinal Stromal Tumours. J Cell Mol Med. 2012;16(2):306-17. PubMed PMID: 21435173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours. AU - Gromova,Petra, AU - Rubin,Brian P, AU - Thys,An, AU - Cullus,Pierre, AU - Erneux,Christophe, AU - Vanderwinden,Jean-Marie, PY - 2011/3/26/entrez PY - 2011/3/26/pubmed PY - 2012/6/26/medline SP - 306 EP - 17 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 16 IS - 2 N2 - 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. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/21435173/ENDOGLIN/CD105_is_expressed_in_KIT_positive_cells_in_the_gut_and_in_gastrointestinal_stromal_tumours_ L2 - https://doi.org/10.1111/j.1582-4934.2011.01315.x DB - PRIME DP - Unbound Medicine ER -