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Updated: Jun 2, 2026

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells
Moorthy P Ponnusamy1, Parthasarathy Seshacharyulu, Arokiapriyanka Vaz
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA. sbatra@unmc.edu.
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.
Insights
MUC4 overexpression in ovarian cancer enriches cancer stem cells, potentially via HER2. Targeting MUC4 may offer a new therapeutic strategy for ovarian cancer stem cells.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
Background:
- Cancer stem cells drive tumor growth, relapse, and metastasis.
- MUC4 is an epithelial cell mucin aberrantly expressed in ovarian cancer, linked to aggressiveness.
- Targeting cancer stem cells requires identifying specific antigens like MUC4.
Purpose of the Study:
- To analyze the cancer stem cell population in MUC4-overexpressed ovarian cancer cells.
- To investigate the role of MUC4 in ovarian cancer stem cell enrichment.
Main Methods:
- Ectopic MUC4 overexpression in SKOV3 ovarian cancer cells.
- Western blot and confocal analysis for MUC4, HER2, CD133, ALDH1, and Shh.
- Flow cytometry (FACS) to quantify cancer stem cell populations (CD133-positive, side population).
Main Results:
- MUC4 overexpression increased HER2 expression in SKOV3 cells.
- Increased side population (0.1%) and CD133-positive cancer stem cells observed.
- MUC4-overexpressing cells formed tumor spheres with CD133, MUC4, HER2, ALDH1, and Shh expression.
Conclusions:
- MUC4 overexpression enriches ovarian cancer stem cells, potentially mediated by HER2.
- This finding supports MUC4 as a target for ovarian cancer stem cell-directed therapies.
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