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
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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