卵巢癌相关成纤维细胞与卵巢癌淋巴结转移的关系The relationship between ovarian cancer associated fibroblasts and lymph node metastases in ovarian cancer
黄在菊;唐慧娟;王泽华;
摘要(Abstract):
目的:探讨肿瘤相关成纤维细胞(CAFs)与卵巢癌临床病理学特征特别是淋巴结转移的关系,研究CAFs在卵巢癌淋巴管生成和淋巴管内皮细胞(LEC)增殖迁移中的作用。方法:免疫组化法检测、计算机图像处理软件分析71例卵巢癌组织间质中α-平滑肌肌动蛋白(α-SMA)阳性面积百分比,以此代表卵巢癌CAFs的数量。用D2-40标记淋巴管内皮细胞,检测淋巴管密度(LVD)。EdU标记法和Transwell迁移实验检测与CAFs共培养前后淋巴管内皮细胞增殖和迁移情况。结果:卵巢癌有淋巴结转移组间质中CAFs百分比明显高于无淋巴结转移组(P=0.024),分别为(29.39±4.32)%和(22.56±6.78)%。卵巢癌间质CAFs数量与淋巴管密度呈正相关(r=0.504,P=0.0003)。与卵巢癌成纤维细胞共培养后,淋巴管内皮细胞增殖增多2.8倍(P<0.0001),迁移增多5.2倍(P<0.0001)。结论:卵巢癌间质成纤维细胞可能通过促进淋巴管内皮细胞增殖、迁移和淋巴管生成,参与卵巢癌的进展和淋巴结的转移。
关键词(KeyWords): 卵巢肿瘤;成纤维细胞;淋巴转移;淋巴管生成;淋巴管内皮细胞
基金项目(Foundation):
作者(Authors): 黄在菊;唐慧娟;王泽华;
DOI: 10.13283/j.cnki.xdfckjz.2012.07.021
参考文献(References):
- [1]Naora H,Montell DJ.Ovarian cancer metastasis:integra-ting insights from disparate model organisms[J].Nat RevCancer,2005,5(5):355-366
- [2]Sundar SS,Zhang H,Brown P,et al.Role of lymphangio-genesis in epithelial ovarian cancer[J].Br J Cancer,2006,94(11):1650-1657
- [3]Miyata Y,Kanda S,Ohba K,et al.Lymphangiogenesis andangiogenesis in bladder cancer:prognostic implicationsand regulation by vascular endothelial growth factors-A,-C,and-D[J].Clin Cancer Res,2006,12(3 Pt 1):800-806
- [4]Cao R,Bjorndahl MA,Religa P,et al.PDGF-BB inducesintratumoral lymphangiogenesis and promotes lymphaticmetastasis[J].Cancer Cell,2004,6(4):333-345
- [5]Kajiya K,Hirakawa S,Ma B,et al.Hepatocyte growth fac-tor promotes lymphatic vessel formation and function[J].EMBO J,2005,24(16):2885-2895
- [6]Kalluri R,Zeisberg M.Fibroblasts in cancer[J].Nat RevCancer,2006,6(5):392-401
- [7]王晓翊,卢实,杨守华,等.卵巢癌相关成纤维细胞的培养及其对癌细胞侵袭力的影响[J].山东医药,2008,48(21):32-34
- [8]Yang S,Cheng H,Cai J,et al.PIGF expression in pre-in-vasive and invasive lesions of uterine cervix is associatedwith angiogenesis and lymphangiogenesis[J].APMIS,2009,117(11):831-838
- [9]Cai J,Tang H,Xu L,et al.Fibroblasts in omentum activa-ted by tumor cells promote ovarian cancer growth,adhe-sion and invasiveness[J].Carcinogenesis,2012,33(1):20-29
- [10]唐慧娟,王晓翊,王泽华.卵巢癌成纤维细胞通过肝细胞生长因子促进癌细胞侵袭作用的研究[J].现代妇产科进展,2009,18(10):721-725
- [11]Kenny HA,Krausz T,Yamada SD,et al.Use of a novel3D culture model to elucidate the role of mesothelialcells,fibroblasts and extra-cellular matrices on adhesionand invasion of ovarian cancer cells to the omentum[J].Int J Cancer,2007,121(7):1463-1472
- [12]Sappino AP,Skalli O,Jackson B,et al.Smooth-muscledifferentiation in stromal cells of malignant and non-ma-lignant breast tissues[J].Int J Cancer,1988,41(5):707-712
- [13]Kuperwasser C,Chavarria T,Wu M,et al.Reconstructionof functionally normal and malignant human breast tis-sues in mice[J].Proc Natl Acad Sci USA,2004,101(14):4966-4971
- [14]Olumi AF,Grossfeld GD,Hayward SW,et al.Carcinoma-associated fibroblasts direct tumor progression of initiatedhuman prostatic epithelium.[J].Cancer Res,1999,59(19):5002-5011
- [15]Sato T,Sakai T,Noguchi Y,et al.Tumor-stromal cellcontact promotes invasion of human uterine cervical car-cinoma cells by augmenting the expression and activa-tion of stromal matrix metalloproteinases[J].GynecolOncol,2004,92(1):47-56
- [16]Ao M,Franco OE,Park D,et al.Cross-talk betweenparacrine-acting cytokine and chemokine pathways pro-motes malignancy in benign human prostatic epithelium[J].Cancer Res,2007,67(9):4244-4253
- [17]Cao Y.Opinion:emerging mechanisms of tumour lym-phangiogenesis and lymphatic metastasis[J].Nat RevCancer,2005,5(9):735-743
- [18]Hwang RF,Moore T,Arumugam T,et al.Cancer-associ-ated stromal fibroblasts promote pancreatic tumor pro-gression.[J].Cancer Res,2008,68(3):918-926
- [19]Sundar SS,Zhang H,Brown P,et al.Role of lymphangio-genesis in epithelial ovarian cancer[J].Br J Cancer,2006,94(11):1650-1657
- [20]Yang S,Zhu X,Cai L,et al.Role of tumor-associatedlymphatic endothelial cells in metastasis:a study of epi-thelial ovarian tumor in vitro[J].Cancer Sci,2010,101(3):679-685