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Published on: September 1, 2010
Tumor stem-like cells isolated from MMQ cells resist to dopamine agonist treatment
Lin Cai1, Jian Chen2, Jianglong Lu1
1Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.
Insights
Pituitary adenoma stem cells resist dopamine agonist treatment, showing lower prolactin and dopamine 2 receptor expression. This resistance may stem from DNA hypermethylation, offering insights into tumor recurrence mechanisms.
Area of Science:
- Endocrinology
- Oncology
- Cell Biology
Background:
- Pituitary adenomas are common tumors, but the role of tumor stem-like cells (TSLCs) in their development and treatment resistance remains unclear.
- Dopamine agonists (DAs) are a primary treatment for prolactinomas, yet some tumors exhibit resistance.
- Understanding TSLCs in pituitary adenomas could elucidate treatment failure and tumor recurrence.
Purpose of the Study:
- To identify and characterize TSLCs in rat prolactinoma (MMQ) cells.
- To investigate the resistance of these putative TSLCs to dopamine agonist (DA) treatment.
- To explore the molecular mechanisms underlying DA resistance in pituitary tumor stem cells.
Main Methods:
- Isolation and culture of sphere-forming cells from rat prolactinoma MMQ cell line.
- Assessment of cell viability and response to dopamine agonist (DA) treatment.
- Quantitative analysis of prolactin (PRL) and dopamine 2 receptor (D2R) expression.
- Investigation of D2R promoter methylation status.
Main Results:
- A subset of sphere-forming cells exhibited TSLC properties and resistance to DA treatment.
- These resistant cells showed increased viability post-DA exposure compared to parental MMQ cells.
- Sphere-forming cells displayed reduced expression of PRL and D2R, potentially due to D2R promoter hypermethylation.
- Differentiated daughter cells regained sensitivity to DA and showed high PRL and D2R expression.
Conclusions:
- Sphere-forming cells isolated from MMQ cells possess TSLC traits and exhibit DA resistance.
- Reduced D2R expression, possibly via DNA hypermethylation, contributes to DA resistance in these pituitary tumor stem cells.
- These findings provide a basis for investigating TSLC-driven mechanisms of pituitary adenoma recurrence and treatment resistance.
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