Galactosylceramide affects tumorigenic and metastatic properties of breast cancer cells as an anti-apoptotic molecule
Autor: | Marek Chadalski, Bartosz Pula, Jaroslaw Suchanski, Alicja M. Kmiecik, Maciej Ugorski, Piotr Dziegiel, Aleksandra Jethon, Tomasz Owczarek |
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Rok vydání: | 2013 |
Předmět: |
Pathology
Lung Neoplasms Mouse Glycobiology lcsh:Medicine Gene Expression Apoptosis Biochemistry Metastasis Small hairpin RNA Mice UGT8 Molecular Cell Biology Basic Cancer Research Breast Tumors Signaling in Cellular Processes RNA Small Interfering lcsh:Science skin and connective tissue diseases Cellular Stress Responses Multidisciplinary Cell Death Obstetrics and Gynecology Antiapoptotic Signaling Animal Models Immunohistochemistry Lipids Ganglioside galactosyltransferase Gene Expression Regulation Neoplastic Oncology Medicine Female medicine.drug Research Article Signal Transduction medicine.medical_specialty Histology Proliferative index Breast Neoplasms Galactosylceramides Biology Model Organisms Cell Line Tumor Breast Cancer medicine Biomarkers Tumor Animals Humans Doxorubicin Sphingolipids lcsh:R Cancers and Neoplasms Lipid Metabolism Transplantation Cell culture Ganglioside Galactosyltransferase Cancer research lcsh:Q Glycolipids |
Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 12, p e84191 (2013) |
ISSN: | 1932-6203 |
Popis: | It was recently proposed that UDP-galactose:ceramide galactosyltransferase (UGT8), enzyme responsible for synthesis of galactosylceramide (GalCer), is a significant index of tumor aggressiveness and a potential marker for the prognostic evaluation of lung metastases in breast cancer. To further reveal the role of UGT8 and GalCer in breast cancer progression, tumorigenicity and metastatic potential of control MDA-MB-231 cells (MDA/LUC) and MDA-MB-231 cells (MDA/LUC-shUGT8) with highly decreased expression of UGT8 and GalCer after stable expression of shRNA directed against UGT8 mRNA was studied in vivo in athymic nu/nu mice. Control MDA/LUC cells formed tumors and metastatic colonies much more efficiently in comparison to MDA/LUC-shUGT8 cells with suppressed synthesis of GalCer after their, respectively, orthotopic and intracardiac transplantation. These findings indicate that UGT8 and GalCer have a profound effect on tumorigenic and metastatic properties of breast cancer cells. In accordance with this finding, immunohistochemical staining of tumor specimens revealed that high expression of UGT8 accompanied by accumulation of GalCer in MDA-MB-231 cells is associated with a much higher proliferative index and a lower number of apoptotic cells in comparison to the MDA/LUC-shUGT8 cells. In addition, it was found that expression of UGT8 in MDA-MB-231 cells increased their resistance to apoptosis induced by doxorubicin in vitro. Therefore, these data suggest that accumulation of GalCer in tumor cells inhibits apoptosis, which would facilitates metastatic cells to survive in the hostile microenvironment of tumor in target organ. |
Databáze: | OpenAIRE |
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