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目的 探讨调控视网膜母细胞瘤(RB)新生血管的相关因素。方法 HXO -Rb- 44细胞株接种到裸鼠后腿皮下,采用免疫组织化学染色方法对RB肿瘤内促血管生成因子(VEGF -A、VEGF- C、VEGF -D)及碱性成纤维细胞生长因子(bFGF),血管内皮细胞膜酪氨酸激酶受体(Flt- 1、Flk- 1、Flt- 4、Tie2及FGFR),转录调控因子Hif 1及促进或抑制细胞外基质降解的基质金属蛋白酶MMP- 2、MMP -7、MMP -9和基质金属蛋白酶抑制因子TIMP- 1、TIMP -2的阳性染色细胞种类、数量、分布及强度进行检测分析。结果 RB肿瘤内有较丰富的毛细血管和小血管,部分肿瘤细胞Hif 1染色阳性,大多数肿瘤细胞高水平表达VEGF,特别是VEGF- D,肿瘤内血管内皮细胞表达Flt -1、Flt- 4和FGFR。肿瘤细胞高水平表达多种基质金属蛋白酶,但不表达基质金属蛋白酶组织抑制因子。结论 VEGF信号传导通路及MMP表达上调、TIMP表达下调在RB肿瘤新生血管形成过程中起重要作用,可考虑作为治疗RB的靶点。
Objective To investigate the regulatory factors of retinoblastoma (RB) neovascularization. Methods HXO-Rb-44 cells were inoculated subcutaneously into the hind leg of nude mice. Immunohistochemical staining was used to detect the growth of angiogenic factors (VEGF-A, VEGF-C, VEGF-D) and basic fibroblasts (BFGF), vascular endothelial cell membrane tyrosine kinase receptors (Flt-1, Flk-1, Flt-4, Tie2 and FGFR), transcriptional regulator Hif 1 and matrix metalloproteinases MMP that promote or inhibit the degradation of extracellular matrix - 2, MMP - 7, MMP - 9 and TIMP - 1, TIMP - 2 were detected by flow cytometry. Results There were abundant capillaries and small vessels in RB tumor. Hif 1 staining was found in some tumor cells. Most of the tumor cells expressed VEGF at high level, especially VEGF-D. Flt-1 and Flt-4 were expressed in vascular endothelial cells And FGFR. Tumor cells express a variety of matrix metalloproteinases at high levels, but do not express inhibitors of matrix metalloproteinase tissue. Conclusions VEGF signaling pathway and MMP expression are upregulated. The down-regulation of TIMP plays an important role in the angiogenesis of RB neoplasia, and may be considered as a target for the treatment of RB.