Molecular biological analysis of pituitary apoplexy induced by hypoxic stimulation in pituitary adenoma

低氧参与了多种生物学过程，在恶性肿瘤中得到了广泛的研究。在良性肿瘤，特别是垂体腺瘤中，缺氧的作用和机制是众所周知的。一些研究表明，与正常脑垂体相比，垂体腺瘤组织血管稀少，血氧饱和度较低，这可能导致缺氧。我们先前的研究表明，层粘连蛋白β2在低氧条件下(1%氧气)而在常氧条件下(21%氧气)不能在HP-75细胞系中孕育。在本研究中，我们用Western blotting进一步研究层粘连蛋白β1、2或3链在低氧和常氧条件下在HP-75细胞中的表达。我们发现，在HP-75细胞系中，只有层粘连蛋白β2在低氧条件下的表达显著高于常氧条件下的表达。对42例(非卒中组30例，卒中组12例)垂体腺瘤石蜡切片进行免疫组织化学染色，研究层粘连蛋白β链的表达。我们发现，只有层粘连蛋白β2的表达与肿瘤大小和中风显著相关，但与侵袭性无关。综上所述，层粘连蛋白β2可以被认为是低氧的替代标志，因为它的水平在低氧条件下显著升高，并且它是侵袭性垂体腺瘤、大腺瘤和中风中主要表达的β链。

Hypoxia, which is involved in a wide range of biological processes, has been extensively investigated in malignant tumors. The role and mechanism of hypoxia in benign tumors, in particular pituitaiy adenomas, is well understood. Some studies indicate that pituitary adenoma tissues are hypovascular and have lower oxygen saturation relative to the normal pituitary gland and suggest that this may induce hypoxia. Our previous study showed that laminin beta 2 mRNA is upregnlated under hypoxic conditions (1% oxygen) but not under normoxic conditions (21% oxygen) in the HP-75 cell line. In the present study, we further investigated the expression of laminin beta 1, 2 or 3 chains, under hypoxic and normoxic conditions in HP-75 cells using Western blotting. We found that only laminin beta 2 had a significantly higher expression under hypoxia than under normoxia in the HP-75 cell line. The expression of laminin beta chains was investigated by fluorescent immunohistochemistry of paraffin-embedded sections of tissue from the pituitary adenomas of 42 cases (30 cases without apoplexy and 12 with apoplexy) categorized according to Knosp grading and tumor size. We found that only laminin beta 2 expression correlated significantly with tumor size and apoplexy, but did not correlate with invasiveness. In conclusion, laminin beta 2 can be regarded as a surrogate marker of hypoxia as its levels are significantly elevated under hypoxic conditions, and it is the predominant beta chain expressed in invasive pituitary adenomas, macroadenomas, and apoplexy.