Abstract:Objective: To observe nerve growth factor (NGF) expression in small cell lung cancer cell line NCI-H466, and explore the possible machanism of its brain metastasis. Methods: Subcellular expression of NGF in NCI-H466 was observed by immunofluorescence staining. MTT and transwell assay were used to evaluate the proliferation and invasion of the cell treated by NGF. Results: The subcellular localization of NGF was cell cycle specific. NGF was located in the nuclei at interphase and on spindle at mitotic phase. Administration of NGF promoted the cell proliferation and invasion. Conclusion: the dependence on NGF may account for the tendency of brain metastasis. The subcellular localization of NGF may be explored as a new target for therapy.
[1] Go PH, Klaassen Z, Meadows MC,et al. Gastrointestinal cancer and brain metastasis: a rare and ominous sign[J]. Cancer,2011,117(16):3630-3640. [2] 刘由军,黄华福,尹生江,等. 肺神经内分泌肿瘤临床表现及CT诊断[J].实用放射学杂志, 2008,24(1):131-132.[3] Ricci A, Mariotta S, Pompili E, et al. Neurotrophin system activation in pleural effusions[J]. Growth Factors,2010,28(4):221-231.[4] Dolle L, EI YazidiBelkoura I, Adriaenssens E, et al. Nerve growth factor overexpression and autocrition loop in breast cell[J]. Oncogene, 2003,22(36):5592-5601.[5] Ricci A, Graziano P, Mariotta S, et al. Neurotrophin system expression in human pulmonary carcinoid tumor[J]. Growth Factors,2005,23(4):303-312.[6] 祝炼,余保平,吴志轩,等. 神经生长因子对原代培养Cajal间质细胞的营养作用[J].胃肠病学和肝病学杂志,2008,17(5):380-382.[7] 张万福,帅晋豪,罗开元.神经生长因子及受体对乳腺癌作用机制的研究进展[J].中国现代普通外科进展,2009,12(1):48-50.[8] Qian Y, Takeuchi S, Chen SJ, et al. Nerve growth factor, brain derived neurotrophic factor and their high affinity receptors are overexpressed in extramammary Paget′s disease[J]. J Cutan Pathol,2010,37(11):1150-1154.[9] Tapia V, Gabler F, Muoz M, et al. Tyrosine kinase A receptor (trkA): a potential marker in epithelial ovarian cancer[J]. Gynecol Oncol, 2011,121(1):13-23.[10] Luo SY, Zhang JM, Li HJ, et al. Effect of nerve growth factor on adhesion and motional abilities of tumor cells and their correlation[J]. Zhonghua Kou Qiang Yi Xue Za Zhi,2010,45(9):531-534.[11] Park MJ, Kwak HJ, Lee HC, et al. Nerve growth factor induces endothelial cell invasion and cord formation by promoting matrix metalloproteinase 2 expression through the phosphatidylinositol 3kinase/Akt signaling pathway and AP-2 transcription factor[J]. J Biol Chem, 2007,282(42):30485-30496.[12] 张志坚,杨勇,于婷,等. NGF及其活化受体P-TrkA在人脑胶质瘤细胞周期中的多靶点分布模式[J].神经解剖学杂志,2007,23(6):577-586.[13] Zhang Z, Yang Y, Gong A, et al. Localization of NGF and TrkA at mitotic apparatus in human glioma cell line U251[J]. Biochem Biophys Res Commun,2005,337(1):68-74.