人脂肪间充质干细胞对宫颈癌细胞的趋化性

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1430 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：探讨人脂肪组织来源的间充质干细胞（hATMSC）对人宫颈癌细胞的趋化性，为将hATMSC研发成为宫颈癌的靶向治疗载体提供实验依据。方法：从剖宫产产妇的皮下脂肪中分离得到hATMSC。用成骨、成脂分化培养基诱导hATMSC，分别采用碱性磷酸酶、油红染色鉴定其多向分化能力；流式细胞仪检测其表面抗原的表达情况；qRT-PCR法分析细胞中OCT-4 mRNA的表达；Transwell实验检测hATMSC向人宫颈鳞癌细胞SiHa、MS751、C33-A、CaSki以及宫颈腺癌细胞Hela迁移的能力。结果：成骨、成脂诱导14 d后，细胞碱性磷酸酶、油红染色均呈阳性；表面抗原CD90、CD44、CD105、HLA-ABC呈阳性表达，而CD34、CD45和HLA-DR呈阴性表达；细胞中OCT-4 mRNA呈高表达；hATMSC表现出明显的向人宫颈癌细胞迁移的特性，其中向C33-A细胞迁移的能力最强。结论：成功分离培养出hATMSC，细胞具有多向分化潜能的干细胞特性。hATMSC对各种人宫颈癌细胞均有明显的趋化性，提示hATMSC可作为一种潜在的细胞载体用于宫颈癌的靶向治疗。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	郑丽红
	刘翊
	朱雪琼

关键词 ：脂肪, 间充质干细胞, 宫颈肿瘤, 趋化

Abstract：Objective: To investigate the chemotaxis of human adipose tissue derived mesenchymal stem cell (hATMSC) to human cervical cancer cells and to provide experimental basis for the development of hATMSC as a target vehicle for the treatment of cervical cancer. Methods: Primary hATMSC from subcutaneous fat of patients undergoing cesarean section was isolated. hATMSC was induced by osteogenic and adipogenic differentiation medium, and using Alkaline Phosphatase, Oil Red O staining respectively to verify the differentiative capacity. The expression of surface antigen and OCT-4 mRNA were detected by flow cytometry and qRT-PCR, respectively. The migration ability of hATMSC to cervical cancer squamous cells SiHa, MS751, C33-A, CaSki and adenocarcinoma cell Hela was detected by Transwell assay. Results: Having been incubated in osteogenic and adipogenic differentiation medium for 14 days, hATMSC was positive by Alkaline Phosphatase and Oil Red O staining. The hATMSC was positive for CD90, CD44, CD105 and HLA-ABC, but negative for CD34, CD45, HLA-DR. OCT-4 mRNA was highly expressed in hATMSC. hATMSC had high motility to migrate to cervical cancer cells, and the migration to C33-A was the strongest among them. Conclusion: hATMSC was successfully isolated and cultured, with the characteristics of stem cells having multi-directional differentiation potential. hATMSC has obvious chemotaxis to different cervical cancer cells, suggesting that hATMSC might be used as a potential carrier for targeting therapy of cervical cancer.

Key words： adipose mesenchymal stem cell uterine cervical neoplasms tropism

收稿日期: 2017-12-18

基金资助:国家自然科学基金资助项目（81671809）；温州市科技计划项目（Y20160123）。

通讯作者: 朱雪琼，教授，Email：zjwzzxq@163.com。

作者简介: 郑丽红（1992-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I5/325

[1] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1): 7-30.
[2] SMITH R A, BROOKS D, COKKINIDES V, et al. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening[J]. CA Cancer J Clin, 2013, 63(2): 88-105.
[3] KATO R, HASEGAWA K, TORII Y, et al. Factors affecting platinum sensitivity in cervical cancer[J]. Oncol Lett, 2015, 10(6): 3591-3598.
[4] ZHU H, CHEN A, LI S, et al. Predictive role of galectin-1 and integrin α5β1 in cisplatin-based neoadjuvant chemotherapy of bulky squamous cervical cancer[J]. Biosci Rep, 2017, 37(5): BSR20170958.
[5] LI L, WANG D, ZHOU J, et al. Characteristics of human amniotic fluid mesenchymal stem cells and their tropism to human ovarian cancer[J]. PLoS One, 2015, 10(4): e0123350.
[6] LI Z, YE Z, ZHANG X, et al. E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice[J]. Oncotarget, 2016, 7(32): 51815-51828.
[7] ABRATE A, BUONO R, CANU T, et al. Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression[J]. Eur J Cancer, 2014, 50(14): 2478-2488.
[8] HO I A, YULYANA Y, SIA K C, et al. Matrix metalloproteinase-1-mediated mesenchymal stem cell tumor tropism is dependent on crosstalk with stromal derived growth factor 1/C-X-C chemokine receptor 4 axis[J]. FASEB J, 2014, 28 (10): 4359-4368.
[9] XU S, MENU E, DE BECKER A, et al. Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo[J]. Stem Cells, 2012, 30(2): 266-279.
[10] MARINI I, SIEGEMUND M, HUTT M, et al. Antitumor activity of a mesenchymal stem cell line stably secreting a tumor-targeted TNF-related apoptosis-inducing ligand fusion protein[J]. Front Immunol, 2017, 8: 536.
[11] KIM N, NAM Y S, IM K I, et al. IL-21-expressing mesenchymal stem cells prevent lethal B-cell lymphoma through efficient delivery of IL-21, which redirects the immune system to target the tumor[J]. Stem Cells Dev, 2015, 24(23): 2808-2821.
[12] AHN J O, LEE H W, SEO K W, et al. Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma[J]. PLoS One, 2013, 8 (9): e74897.
[13] 林琳, 孙雯, 王丽双. 间充质干细胞对人HeLa宫颈癌细胞生长的影响[J]. 中华医学杂志, 2015, 95(15): 1175-1178.
[14] 刘华, 陈亚娜, 郑燕, 等. 人脐带间充质干细胞对宫颈癌Hela细胞增殖的影响[J]. 山东大学学报(医学版), 2013, 51 (6): 29-33.
[15] 刘世凯, 宋莉莉, 曾赛田, 等. 人脐带间充质干细胞对宫颈癌Hela细胞增殖特性的影响[J]. 中国组织工程研究, 2015, 19(45): 7274-7278.
[16] CHO J A, PARK H, KIM H K, et al. Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line[J]. Cancer, 2009, 115(2): 311-323.