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15 April 2017 : Laboratory Research  

Expression of Stem Cell Markers and Dopamine D2 Receptors in Human and Rat Prolactinomas

Zhichao Gao1BE, Lin Cai1CE, Jianglong Lu1DF, Chengde Wang1DF, Qun Li1EF, Jian Chen2BF, Xiaoxiao Song2EF, Xianbin Chen1DE, Linlin Zhang3DE, Weiming Zheng1BDF*, Zhipeng Su1ABFG

DOI: 10.12659/MSM.901154

Med Sci Monit 2017; 23:1827-1833

Abstract

BACKGROUND: Dopamine agonists (DAs) are the first-line treatment for prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem-like cells (TSLCs) are associated with the tolerance to radiotherapy and chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to characterize the expression pattern of stem cell markers and D2R in human and rat prolactinomas.

MATERIAL AND METHODS: Human prolactinoma specimens (n=14) were obtained from patients with surgical resection. The xenograft model of rat prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were confirmed by immunohistochemical staining of tumor sections, and the expression of serum PRL was measured by ELISA. The expression of stem cell markers (CD133, Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by immunofluorescence. The proportion of CD133-expressing cells after DA treatment was evaluated by flow cytometry in vitro.

RESULTS: We found that a small subpopulation of cells expressing stem cell markers existed both in human and rat prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R expression. Conversely, the D2R-expressing cells showed negative CD133 expression. The proportion of CD133-expressing cells in surviving tumor cells was significantly increased after DA treatment.

CONCLUSIONS: Our results confirmed the existence of cells expressing stem cell markers in human and rat prolactinomas. Additionally, the CD133-expressing cells might resist DA therapy due to the lack of D2R expression.

Keywords: Dopamine Agonists, prolactinoma, Receptors, Dopamine D2, Stem Cells, Drug Resistance

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750