MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells
Open Access
- 26 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Ovarian Research
- Vol. 4 (1), 7-10
- https://doi.org/10.1186/1757-2215-4-7
Abstract
Background Recent evidence has suggested that the capability of cancer to grow, propagate and relapse after therapy is dependent on a small subset of the cell population within the tumor, called cancer stem cells. Therefore, this subpopulation of cells needs to be targeted with different approaches by identification of unique stem-cell specific target antigens. One of the well known tumor antigens is the epithelial cell mucin MUC4, which is aberrantly expressed in ovarian cancer as compared to the normal ovary and plays a pivotal role in the aggressiveness and metastasis of ovarian cancer cells. In the present study, we aimed to analyze the cancer stem cell population in MUC4 overexpressed ovarian cancer cells. Methods MUC4 was ectopically overexpressed in SKOV3 ovarian cancer cells. Western blot analysis was performed for MUC4, HER2, CD133, ALDH1 and Shh expression in MUC4 overexpressed cells. Confocal analysis of MUC4, HER2 and CD133 was also done in the MUC4 overexpressed cells. CD133 and Hoechst33342 dye staining was used to analyze the cancer stem cell population via FACS method in SKOV3-MUC4 cells. Results MUC4 overexpressed SKOV3 cells showed an increased expression of HER2 compared to control cells. MUC4 overexpression leads to increased (0.1%) side population (SP) and CD133-positive cancer stem cells compared to the control cells. Interestingly, the tumor sphere type circular colony formation was observed only in the MUC4 overexpressed ovarian cancer cells. Furthermore, the cancer stem cell marker CD133 was expressed along with MUC4 in the isolated circular colonies as analyzed by both confocal and western blot analysis. HER2 and cancer stem cell specific marker ALDH1 along with Shh, a self-renewal marker, showed increased expression in the isolated circular colonies compared to MUC4-transfected cells. Conclusion These studies demonstrate that MUC4 overexpression leads to an enriched ovarian cancer stem cell population either directly or indirectly through HER2. In future, this study would be helpful for MUC4-directed therapy for the ovarian cancer stem cell population.Keywords
This publication has 27 references indexed in Scilit:
- MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cellsOncogene, 2010
- MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cellsBritish Journal of Cancer, 2008
- HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasionOncogene, 2008
- MUC4 Mucin Interacts with and Stabilizes the HER2 Oncoprotein in Human Pancreatic Cancer CellsCancer Research, 2008
- Ovarian cancer: emerging concept on cancer stem cellsJournal of Ovarian Research, 2008
- Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)Laboratory Investigation, 2006
- Tumour stem cells and drug resistanceNature Reviews Cancer, 2005
- Mucins in cancer: protection and control of the cell surfaceNature Reviews Cancer, 2004
- Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance.2001
- Mucin gene expression in ovarian cancers.1998