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Verfasst von:Cai, Chen [VerfasserIn]   i
 Itzel, Timo [VerfasserIn]   i
 Gaitantzi, Haristi [VerfasserIn]   i
 Torre, Carolina de la [VerfasserIn]   i
 Birgin, Emrullah [VerfasserIn]   i
 Betge, Johannes [VerfasserIn]   i
 Gretz, Norbert [VerfasserIn]   i
 Teufel, Andreas [VerfasserIn]   i
 Rahbari, Nuh Nabi [VerfasserIn]   i
 Ebert, Matthias [VerfasserIn]   i
 Breitkopf-Heinlein, Katja [VerfasserIn]   i
Titel:Identification of liver-derived bone morphogenetic protein (BMP)-9 as a potential new candidate for treatment of colorectal cancer
Verf.angabe:Chen Cai, Timo Itzel, Haristi Gaitantzi, Carolina de la Torre, Emrullah Birgin, Johannes Betge, Norbert Gretz, Andreas Teufel, Nuh N. Rahbari, Matthias P. Ebert, Katja Breitkopf-Heinlein
E-Jahr:2022
Jahr:January 2022
Umfang:11 S.
Fussnoten:First published: 28 November 2021 ; Gesehen am 07.12.2022
Titel Quelle:Enthalten in: Journal of cellular and molecular medicine
Ort Quelle:Hoboken, NJ : Wiley-Blackwell, 2000
Jahr Quelle:2022
Band/Heft Quelle:26(2022), 2, Seite 343-353
ISSN Quelle:1582-4934
Abstract:Colorectal cancer (CRC) is a high-incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)-9 and to find out whether the application of BMP-9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP-target gene ID1, especially in combination with low expression of the BMP-inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T-Orgs) and corresponding non-malignant areas (N-Orgs) of three patients. The N-Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP-9 stimulation of organoids promoted an enrichment of tumour-suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP-9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1. In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP-9 enhances this ratio, even in the presence of noggin. Thus, BMP-9 is identified as a novel target for the development of improved anti-cancer therapies of patients with CRC.
DOI:doi:10.1111/jcmm.17084
URL:kostenfrei: Volltext: https://doi.org/10.1111/jcmm.17084
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.17084
 DOI: https://doi.org/10.1111/jcmm.17084
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:bone morphogenetic protein-9
 colorectal cancer
 ID1
 noggin
K10plus-PPN:1826462627
Verknüpfungen:→ Zeitschrift
 
 
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