【作者】 张丹芳； 张诗武； 郭华； 张文治； 赵秀兰； 孙保存；

【Author】 Zhang Dan-Fang Zhang Shi- Wu Guo Hua Zhang Wen-Zhi Zhao Xiu-Lan Sun Bao-Cun

【机构】 天津市肿瘤医院病理科； 天津市环湖医院细胞室； 天津医科大学病理教研室；

【摘要】 目的:研究缺血缺氧环境下肿瘤生长、血液供应模式及浸润转移相关蛋白表达的变化,阐述血管介入治疗黑色素瘤远期效果不理想的相关分子机制。方法:建立小鼠缺血后肢黑色素瘤移植瘤模型,观察缺血环境下的肿瘤生长情况,计数各种血液供应模式,免疫组化染色检测HIF-1 α、 MMP-2、MMP-9及VEGF等在正常和缺氧环境中肿瘤细胞表达。结果:肿瘤生长早期,缺血组的肿瘤生长速度比未缺血组慢(t=0．858,P=0．039),但最终两组肿瘤的平均体积差异无统计学意义(P=0．431);HIF-1α、MMP-2、MMP-9 和VEGF也在缺血组瘤细胞内高表达(P=0．036,0．015,0．008 和0．019),缺血组内血管生成拟态数量和肿瘤体积与HIF-1 α水平呈正相关(r=0．472,0．391,P=0．015,0．050)。结论:在缺氧环境中,黑色素瘤细胞能够通过HIF-1 α上调 MMP-2、MMP-9及VEGF等蛋白表达,肿瘤细胞更富有侵袭性,同时促进肿瘤血管生成拟态的形成。更多还原

【Abstract】 Objective: Hypoxic can enhance tumor cell invasion and metastasis. The reason and the molecular mechanism are still not clear. Methods: In our study, mouse melanoma B16 cells were inoculated into mouse is-chemic limbs and non-ischemic controls and the engrafted melanomas were subsequently observed respectively. Vasculogenic mimicry in melanoma cells of the two groups was counted and the expression of HIF-1 α, MMP-2, MMP-9 and VEGF were assessed by immunohistochemi-cal staining. Formalin-fixed, paraffin-embedded tissues were used in immunohistochemical staining. Results: In the early stage of engrafted melanoma growth, the sizes of melanomas in ischemic limbs increased more slowly than in the controls. However, later there was no obvious difference in their sizes. The number of vasculogenic mimicry in melanoma of the ischemic group was more than in the controls (P=0.039). Similarly, the expression of HIF-1 α, MMP-2, MMP-9 and VEGF was higher in the ischemic group than in the controls (P=0.036, 0.015, 0.008 and 0. 019 respectively). There was a positive correlation between HIF-1 pppppp expression and vasculogenic mimicry number in the ischemic group ( r = 0.472, 0.391, P = 0.015,0.050). Conclusion: Melanoma cells in a hypoxic microenvironment improved HIF-1 α expression to upregulate the expressions of MMP-2, MMP-9 and VEGF, which enhance the invasion ability of melanoma cells to grow and metastasize as well as prompt the formation of vascuiogenic mimicry to acquire an adequate blood supply.更多还原