切换至 "中华医学电子期刊资源库"

中华肝脏外科手术学电子杂志 ›› 2013, Vol. 02 ›› Issue (03) : 194 -199. doi: 10.3877/cma.j.issn.2095-3232.2013.03.012

所属专题: 文献

基础研究

肝癌相关成纤维细胞对肝细胞肝癌影响的实验研究
华学锋1, 李团结2, 贾昌昌1, 陈冠中1, 郭宇1, 邱东波3, 台艳3, 张琪3, 陈规划1,()   
  1. 1. 510530 广州,中山大学附属第三医院岭南医院器官移植科
    2. 安徽医科大学第一附属医院普外科
    3. 广东省肝脏疾病研究重点实验室
  • 收稿日期:2013-04-01 出版日期:2013-06-10
  • 通信作者: 陈规划
  • 基金资助:
    广东省自然科学基金(S2012040006483)

Effect of hepatocellular carcinoma associated fibroblasts to hepatocellular carcinoma

Xue-feng HUA1, Tuan-jie LI2, Chang-chang JIA1, Guan-zhong CHEN1, Yu GUO1, Dong-bo QIU3, Yan TAI3, Qi ZHANG3, Gui-hua CHEN1,()   

  1. 1. Organ Transplantation Center, Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510530, China
  • Received:2013-04-01 Published:2013-06-10
  • Corresponding author: Gui-hua CHEN
  • About author:
    Corresponding author: CHEN Gui-hua, Email:
引用本文:

华学锋, 李团结, 贾昌昌, 陈冠中, 郭宇, 邱东波, 台艳, 张琪, 陈规划. 肝癌相关成纤维细胞对肝细胞肝癌影响的实验研究[J/OL]. 中华肝脏外科手术学电子杂志, 2013, 02(03): 194-199.

Xue-feng HUA, Tuan-jie LI, Chang-chang JIA, Guan-zhong CHEN, Yu GUO, Dong-bo QIU, Yan TAI, Qi ZHANG, Gui-hua CHEN. Effect of hepatocellular carcinoma associated fibroblasts to hepatocellular carcinoma[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2013, 02(03): 194-199.

目的

探讨肝癌相关成纤维细胞(hCAF)对肝细胞肝癌(肝癌)转移的影响。

方法

分别将hCAF和正常成纤维细胞(NF)培养2~3 d,行免疫荧光染色,观察hCAF和NF细胞中α-平滑肌肌动蛋白(α-SMA)、成纤维细胞表面蛋白(FSP)、成纤维细胞活化蛋白(FAP)、波形蛋白(vimentin)的表达情况。通过hCAF与MHCC97L-绿色荧光蛋白(GFP)、HepG2-GFP肝癌细胞共培养及划痕实验,观察hCAF对肝癌细胞的形态变化的影响及其对肝癌侵袭转移能力的作用。

结果

hCAF和NF细胞均表达α-SMA、FSP、FAP、vimentin,但hCAF表达α-SMA与FAP的水平明显高于NF。hCAF与肝癌细胞共培养至96 h,MHCC97L-GFP细胞生长由典型的抱团样成簇生长,变成分散呈播散样生长;HepG2-GFP细胞由多角形的上皮细胞形态转变为长梭形的间质细胞形态。MHCC97L-GFP、HepG2-GFP肝癌细胞与hCAF共培养5 d后划痕明显较NF组缩小。

结论

hCAF能加速肝癌细胞发生类似上皮细胞间质转型的变化,增强肝癌细胞侵袭转移能力。

Objective

To investigate the effect of hepatocellular carcinoma(HCC) associated fibroblasts (hCAF) to the metastasis of HCC.

Methods

The hCAF and normal fibroblasts (NF) cells were cultured for 2 to 3 days and then stained by immunofluorescence. The expression of α-smooth muscle actin(α-SMA), fibroblast surface protein (FSP), fibroblast activation protein (FAP) and vimentin of hCAF and NF cells were observed. The effect of hCAF to cell morphology change and invasion and metastasis of HCC were observed through co-culture and scratch test of hCAF and MHCC97L-green fluorescent protein(GFP), HepG2-GFP HCC cells.

Results

The expression of α-SMA, FSP, FAP and vimentin were all observed in the hCAF and NF cells. The expression level of α-SMA and FAP in hCAF cells were obviously higher compared with the NF. The hCAF and HCC cells were co-cultured for 96 hours. The typical clustering growth of MHCC97L-GFP cells changed to disseminated growth. The polygon shape of epithelial cell of HepG2-GFP cell changed to spindle shape of interstitial cell. The scratch of MHCC97L-GFP, HepG2-GFP cells and hCAF cells after 5 days co-culture lessened obviously, compared with NF cells.

Conclusion

The hCAF cells can promote the transformation of epithelial cells into interstitial cells and enhance the invasion and metastasis of HCC cells.

图1 荧光显微镜观察hCAF和NF的α-SMA、FSP、FAP、波形蛋白表达图像
图2 荧光显微镜观察hCAF、NF和MHCC97L-GFP共培养96 h图像
图3 荧光显微镜观察hCAF、NF和HepG2-GFP共培养96 h图像
图4 荧光显微镜观察hCAF与MHCC97L-GFP共培养5 d后划痕实验图像
图5 荧光显微镜观察HepG2-GFP与hCAF共培养5 d后划痕实验图像
[1]
Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer,2006, 6(5):392-401.
[2]
Mueller MM, Fusenig NE. Friends or foes-bipolar effects of the tumour stroma in cancer. Nat Rev Cancer, 2004, 4(11):839-849.
[3]
Tlsty TD. Stromal cells can contribute oncogenic signals. Semin Cancer Biol, 2001, 11(2):97-104.
[4]
Barsky SH, Green WR, Grotendorst GR, et al. Desmoplastic breast carcinoma as a source of human myofibroblasts. Am J Pathol, 1984, 115(3):329-333.
[5]
Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer, 2003, 3(6):401-410.
[6]
Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev, 2003, 83(3):835-870.
[7]
Coussens LM, Werb Z. Inflammation and cancer. Nature, 2002, 420(6917):860-867.
[8]
Polanska UM, Acar A, Orimo A. Experimental generation of carcinoma-associated fibroblasts (CAFs) from human mammary fibroblasts. J Vis Exp, 2011, 25(56):e3201.
[9]
Barsky SH, Green WR, Grotendorst GR, et al. Desmoplastic breast carcinoma as a source of human myofibroblasts. Am J Pathol, 1984, 115(3):329-333.
[10]
Olumi AF, Grossfeld GD, Hayward SW, et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res, 1999, 59(19):5002-5011.
[11]
Li L, Dragulev B, Zigrino P, et al. The invasive potential of human melanoma cell lines correlates with their ability to alter fibroblast gene expression in vitro and the stromal microenvironment in vivo. Int J Cancer, 2009, 125(8):1796-1804.
[12]
Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 2005, 121(3):335-348.
[13]
Mazzocca A, Dituri F, Lupo L, et al. Tumor-secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts. Hepatology, 2011, 54(3):920-930.
[14]
Dimanche-Boitrel MT, Vakaet L Jr, Pujuguet P, et al. In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts. Int J Cancer, 1994, 56(4):512-521.
[15]
Olaso E, Santisteban A, Bidaurrazaga J, et al. Tumor-dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis. Hepatology, 1997, 26(3):634-642.
[16]
Vered M, Dayan D, Yahalom R, et al. Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma. Int J Cancer, 2010, 127(6):1356-1362.
[17]
Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res, 2010, 70(17):6945-6956.
[18]
Lee TK, Poon RT, Yuen AP, et al. Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1alpha-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma. Clin Cancer Res, 2006, 12(23):6910-6919.
[19]
Alonso SR, Tracey L, Ortiz P, et al. A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res, 2007, 67(7):3450-3460.
[1] 刘昌玲, 张金丽, 张志, 李孝建, 汤文彬, 胡逸萍, 陈宾, 谢晓娜. 负载人脂肪干细胞外泌体的甲基丙烯酰化明胶水凝胶对人皮肤成纤维细胞增殖和迁移的影响[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 517-525.
[2] 宋勤琴, 李双汝, 李林, 杜鹃, 刘继松. 间充质干细胞源性外泌体在改善病理性瘢痕中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 550-553.
[3] 李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[4] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[5] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[6] 公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[7] 李一帆, 朱帝文, 任伟新, 鲍应军, 顾俊鹏, 张海潇, 曹耿飞, 阿斯哈尔·哈斯木, 纪卫政. 血GP73水平在原发性肝癌TACE疗效评价中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 825-830.
[8] 刘敏思, 李荣, 李媚. 基于GGT与Plt比值的模型在HBV相关肝细胞癌诊断中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 831-835.
[9] 焦振东, 惠鹏, 金上博. 三维可视化结合ICG显像技术在腹腔镜肝切除术治疗复发性肝癌中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 859-864.
[10] 张润锦, 阳盼, 林燕斯, 刘尊龙, 刘建平, 金小岩. EB病毒相关胆管癌伴多发转移一例及国内文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 865-869.
[11] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[12] 袁雨涵, 杨盛力. 体液和组织蛋白质组学分析在肝癌早期分子诊断中的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 883-888.
[13] 吴警, 吐尔洪江·吐逊, 温浩. 肝切除术前肝功能评估新进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 889-893.
[14] 邓万玉, 陈富, 许磊波. 肝硬化与非肝硬化乙肝相关性肝癌患者术后无复发生存比较及其影响因素分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 670-674.
[15] 何慧玲, 鲁祖斌, 冯嘉莉, 梁声强. 术前外周血NLR和PLR对结肠癌术后肝转移的影响[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 682-687.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?