Expression And Significance Of NRP-1 In Xenografts Of Lung Cancer Cell In Nude Mouse

[Objective] To establish angiogenesis model of xenografts of lung cancer cell in nude mouse and to study the expression of the neuropilin-1(NRP-1) protein in tumors and its role in progression and angiogenesis of lung cancer.[Methods] Human lung adenocarcinoma cells A549 were analyzed for expression of vascular endothelial growth factor-165(VEGF165) mRNA using RT-PCR in vitro. Two groups of nude mice were subcutaneously inoculated with A549 at different tumor-loading time. Two groups of xenografts were identified by hematoxylin and eosin (H&E) staining. And two groups of microvessel density (MVD) were analyzed meanwhile. Two groups of tumors were analyzed for expression of NRP-1 protein and their mean absorbency by using immuno-histochemistry and automatic image analysis system respectively.[Results] A549 cell line expressed VEGF165 mRNA, and xenografts of A549 in nude mice were successfully established and identified by H&E staining. The atypia of cancer cells and angiogenesis were seen in two groups. Two groups of MVD are 13.06±1.58,23.61±3.11(vessels/mm2)(P<0.01). NRP-1 protein was expressed in cytoplasm of vascular endothelium cells and partial tumor cells. Two groups of mean absorbency of NRP-1 were 0.1095±0.0228, 0.1784±0.0151 (P<0.01).[Conclusion] The angiogenesis models of xenografts in nude mice with lung cancer cell A549 expressing VEGF165 mRNA at different tumor-loading time are establed successfully. The expression of NRP-1 protein and MVD are increased with the tumor progression. The results demonstrate that NRP-1 in lung cancer is related to angiogenesis. Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal guidance that bound members of the semaphorin/ collapsin family and guide correct location of axon in neural development. NRP-1 is also expressed in endothelial cells and is believed to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF-independent fashion in tumor angiogenesis, growth and metastasis.