酪氨酸激酶受体阳性单核细胞对卵巢肿瘤生长及微血管、淋巴管生成作用研究被引量：1

The effects of tie2^+-U937 on proliferation, angiogenesis and lymphangiogenesis of ovarian carcinoma

导出

摘要目的探讨酪氨酸激酶受体阳性(Tie2+)的单核细胞(Tie2+-U937)对裸鼠移植瘤生长和微血管、淋巴管生成的作用。方法 2013年1月至2014年2月在上海交通大学医学院构建裸鼠卵巢肿瘤皮下和原位模型,转染Tie2+-U937和NC-U937,分别将转染了荧光的人卵巢癌细胞系(SKOV3ip1-luc)与Tie2+-U937或者NC-U937按1:10比例混匀,注入裸鼠皮下和卵巢包膜下,单独的SKOV3作为阴性对照组,观察裸鼠成瘤时间和肿瘤大小;免疫组化检测肿瘤微血管和淋巴管的表达。结果 Tie2+-U937能够促进裸鼠皮下和原位移植瘤生长。皮下成瘤模型:注射后第8、21天Tie2组肿瘤总荧光强度值大于其他两组(P<0.05)。裸鼠于21d处死并称其肿瘤重量,Tie2组(0.43±0.16)g,U937组(0.18±0.04)g,Control组(0.13±0.08)g,Tie2肿瘤重量较其他两组重(P<0.05);Tie2组免疫组化CD31的表达明显大于其余两组(P<0.05);原位模型:注射后第14、35天Tie2组肿瘤总荧光强度值大于其余两组(P<0.05);Tie2组免疫组化CD31和LYVE-1的表达明显大于其余两组(P<0.05)。结论 Tie2+单核细胞能够促进卵巢肿瘤裸鼠皮下、原位移植瘤的生长,并且其促进肿瘤增殖的作用与微血管和淋巴管生成有关。 Objective Aim to explore the effects of TieT-U937 cells on proliferation and its efftcts on angiogenesis and lymphangiogenesis of ovarian carcinoma in nude mice.Methods The ovarian carcinoma models were constructed between Janary 2013 and Fedruary 2014 in Shanghai Jiaotong University School of Medicine Human Tie2＋-U937 cells and NC-U937 cells were cultured by transfection. Nude mice were injected with mix of human SKOV3ipl-luc cells and Tie2＋-U937 ceils or NC-U937 cells by 1：10 in the subcutaneous models and orthotopic models . SKOV3 ceils were injected as control group. The proliferation time, tumor size, CDS1 and LYVE-1 expression of ovarian carcinoma were detected.Results The results revealed that Tie2 led to an enhancement on tumor proliferation. In the subcutaneous models： Tie2 led to an enhancement on tumor proliferation, compared with U937 group and control group on the 8th day and 21st day. The tumor weights of different groups on the 21st day ： Tie2 group（0.43±0.16）g, U937 group （0.18±0.04）g, control group （0.13 ±0.08）g（P〈0.05）.In the orthotopic models： Tie2 led to an enhancement on tumor proliferation, compared with U937 group and control group on the 14th day and 35th day. Tie2 group was illustrated the highest intratumoral CD31 and LYVE- 1 expression level, as compared with the other groups （P〈0.05）. Conclusion Tie2＋-U937 cells can promote ovarian carcinoma proliferation through angiogenesis and lymphangiogenesis in nude mice.

作者朱沁怡吴丽吴小丽王凯汪希鹏

机构地区同济大学附属第一妇婴保健院妇科

出处《中国实用妇科与产科杂志》 CAS CSCD 北大核心 2014年第10期775-779,共5页 Chinese Journal of Practical Gynecology and Obstetrics

基金国家自然基金(81372787 81072136) 上海市新百人计划(XBR2011065)

关键词酪氨酸激酶受体阳性的单核细胞卵巢肿瘤血管转移淋巴转移 TieT-U937 ovarian carcinoma angiogenesis lymphangiogenesis

分类号 R713.4 [医药卫生—妇产科学]

引文网络
相关文献

参考文献20

1Ochiumi T, Tanaka S, Oka S, et al. Clinical significance of angio- poietin-2 expression at the deepest invasive tumor site of ad- vanced coloreetal carcinoma [J]. Int J Oncol,2004,24(3):539- 547.
2吴丽,王凯,吴小丽,胡婧,赵肖波,汪希鹏.卵巢上皮性癌中表达Tie2单核巨噬细胞的研究[J].中国实用妇科与产科杂志,2013,29(8):657-661. 被引量：2
3吴丽,汪希鹏.表达Tie2单核巨噬细胞在肿瘤进展中的作用[J].中国免疫学杂志,2013,29(4):426-429. 被引量：2
4Ai Z, Yin L, Zhou X, et al. Inhibition of survivin reduces cell pro- liferation and induces apoptosis in human endometrial can- cer[J]. Cancer,2006,107(4):746-756.
5lmanishi Y, Hu B, Jarzynka MJ, et al. Angiopoietin-2 stimulates breast cancer metastasis through the alpha(5)beta(1) integrin- mediated pathway [ J ]. Cancer Res,2007,67(9):4254-4263.
6Dumont DJ, Anderson L, Breitman ML, et al. Assignment of the endothelial-specific protein receptor tyrosine kinase gene (TEK) to human chromosome 9-21 [J]. Genomics,1994,23(2): 512-513.
7Fiedler U, Krissl T, Koidl S, et al. Angiopoietin- 1 and angiopoi- etin-2 share the same binding domains in the Tie-2 receptor in- volving the first Ig-like loop and the epidermal growth factor- like repeats[J]. J Biol Chem,2003,278(3):1721-1727.
8Kioi M, Vogel H, Schultz G, et al. Inhibition of vasculogenesis,but not angiogenesis, prevents the recurrence of glioblastoma af- ter irradiation in mice [ J ]. J Clin Invest,201 O, 120(3):694-705.
9Du R, Lu KV, Petritsch C, et aL HIF1 alpha induces the recruit- ment of bone marrow-derived vascular modulatory ceils to regu- late tumor angiogenesis and invasion [J]. Cancer Ce11,2008,13 (3):206-220.
10Pucci F, Venneri MA, Biziato D, et al. A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing mono- cytes, blood "resident" monocytes, and embryonic macro- phages suggests common functions and developmental relation- ships[J]. Blood,2009,114(4):901-914.

二级参考文献38

1Dumont D J, Anderson L, Breitman M L et al. Assignment of the endothelial-specific protein receptor tyrosine kinase gene (TEK) to human chromosome 9p21 [ J]. Genomics, 1994 ; 23 (2) :512-513.
2Partanen J, Armstrong E, Makela T Pet al. A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains [ J ]. Mol Cell Biol, 1992; 12 (4) : 1698-1707.
3Davis S, Aldrich T H, Jones P F et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning [J]. Cell, 1996;87(7) :1161-1169.
4Maisonpierre P C, Suri C, Jones P F et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis [ J ]. Science , 1997 ;277(5322) :55-60.
5Holash J, Maisonpierre P C, Compton D et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF [ J ]. Science , 1999 ;284 (5422) : 1994-1998.
6Lobov I B, Brooks P C, Lang R A. Angiopoietin-2 displays VEGF- dependent modulation of capillary structure and endothelial cell survival in vivo[J]. Proc Nail Acad Sci USA, 2002;99 (17): 11205-11210.
7De Palma M, Venneri M A, Galli R et al. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors [ J ]. Cancer Cell, 2005 ; 8 (3) :211-226.
8De Palma M, Venneri M A, Roca C et al. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells[ J]. Nat Med, 2003 ;9(6) :789-795.
9Gordon S, Taylor P R. Monocyte and macrophage heterogeneity[J]. Nat Rev Immunol,2005 ; 5 (12) :953-964.
10Venneri M A, De Palma M, Ponzoni M et al. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer[J]. Blood, 2007 ;109(12) :5276-5285.