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19 August 2015 : Laboratory Research  

Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas

Shouchun LiABC, Zhiwen ZhangBC, Jinghui XueCD, Xiaoming GuoDE, Shuli LiangEF, Aijun LiuFG

DOI: 10.12659/MSM.894205

Med Sci Monit 2015; 21:2433-2438

Abstract

BACKGROUND: Pituitary adenoma is a common intracranial tumor in neurosurgery. Some pituitary adenomas have the characteristics of invasive growth make them unable to be removed completely by surgery leading to easy relapse. Discoidin domain receptor l (DDR1) is a new kind of tyrosine kinase receptor on the cell surface. DDR1 can be activated by tumor microenvironment signal in tumorigenesis, increasing MMP-2/9 expression and promoting the invasive ability of tumor cells. Anoxia can promote tumor growth and metastasis. This study investigated the impact of anoxic environment DDR1 expression in pituitary adenoma.

MATERIAL AND METHODS: A primary hypoxia pituitary adenoma cell model was established and treated with DDR1 inhibitor nilotinib. Real-time PCR and Western blot were used to detect DDR1 mRNA and protein expression. ELISA was used to detect MMP-2/9 changes. MTT method was used to detect pituitary adenoma cell proliferation. We used a transwell chamber to determine pituitary adenoma cell invasion ability.

RESULTS: DDR1 mRNA and protein were significantly overexpressed under hypoxia (P<0.05). MMP-2 and MMP-9 expression was obviously increased in supernatant (P<0.05). Pituitary adenoma cell proliferation and invasive ability improved markedly under hypoxia (P<0.05). Nilotinib could reduce DDR1 expression, decrease MMP-2 and MMP-9 expression, and inhibit pituitary adenoma cells proliferation and invasion.

CONCLUSIONS: Hypoxia can increase DDR1 expression in pituitary adenoma cells, leading to improved MMP-2 and MMP-9 secretion, and promoting pituitary adenoma cell proliferation and invasion.

Keywords: Adenoma - pathology, Antineoplastic Agents - pharmacology, Cell Hypoxia - physiology, Cell Proliferation - drug effects, Gene Expression - drug effects, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase 9 - metabolism, Neoplasm Proteins - metabolism, Pituitary Neoplasms - pathology, Protein Kinase Inhibitors - pharmacology, Protein-Tyrosine Kinases - antagonists & inhibitors, Pyrimidines - pharmacology, RNA, Messenger - metabolism, RNA, Neoplasm - metabolism, Receptor Protein-Tyrosine Kinases - metabolism, Tumor Cells, Cultured, tumor microenvironment

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