妇科肿瘤相关间充质干细胞研究进展

发布时间：2018-04-03 18:38

本文选题：间充质干细胞　切入点：宫颈肿瘤　出处：《中华肿瘤防治杂志》2015年12期

【摘要】：目的总结目前妇科肿瘤相关间充质干细胞(mesenchymal stem cells,MSCs)的研究进展。方法应用PubMed和CNKI期刊全文数据库检索系统,以"宫颈肿瘤、卵巢肿瘤、子宫体肿瘤、外阴肿瘤、阴道肿瘤、输卵管肿瘤和间充质干细胞"为关键词,检索2000-01-01-2014-10-31的相关文献,纳入标准:1)MSCs相关文献;2)正常组织来源的MSCs与肿瘤;3)肿瘤组织中的MSCs;4)妇科肿瘤组织中的MSCs。根据纳入标准符合分析的文献29篇。结果 1)MSCs是一种机体内部间质内广泛存在的非造血系成体干细胞,可分化为骨骼、软骨和脂肪细胞等。2)正常组织来源的MSCs能调控肿瘤生长,起抑制还是促进作用与宿主免疫功能状态、肿瘤细胞类型和所处微环境等因素有关。肿瘤相关的炎症环境能改变正常MSCs的功能,使之获得高效招募炎性单核及巨噬细胞的能力,从而达到促进肿瘤生长的目的。MSCs能分化为成纤维细胞,为肿瘤进展提供结构和功能支持,形成血管细胞,促进微血管形成,形成间质网络改善肿瘤微环境,从而促进肿瘤的增殖。3)肿瘤组织中也存在MSCs,在肿瘤增殖调控中起重要作用,在肺癌、胃癌和骨肉瘤等实体瘤中得到分离和验证。4)妇科常见恶性肿瘤中的宫颈癌、卵巢癌和子宫内膜癌组织中均能分离出具有多向分化潜能的MSCs。宫颈癌组织标本的MSCs亚群,形态似成纤维细胞,呈克隆样增殖,免疫表型为CD13、CD29、CD44、CD105和HLA-I阳性,细胞保持正常的核型,在适当的诱导条件下,这些细胞能够分化成骨细胞等;宫颈癌相关MSCs能促进肿瘤细胞增殖,机制与血管生成和上皮间质转化相关。卵巢癌腹水和肿瘤组织中均可分离出MSCs,高表达CD44、MMP9和Oct4,具有正常的形态和核型,能分化成脂肪、软骨和骨,本身无致瘤性,能通过增加肿瘤干细胞的数目以促进肿瘤的生长。子宫内膜基质中的MSCs可以长期增殖,有分化和克隆形成能力。异位子宫内膜的MSCs侵袭和浸润能力更强。子宫内膜癌中分离出的侧群细胞,能分化成MSCs,可以在裸鼠体内形成大的浸润性肿瘤,具有丰富的细胞外基质,有肿瘤细胞和间质细胞样细胞。但目前鲜见内膜癌相关的MSCs调控内膜癌细胞增殖的研究报道。结论通过对妇科肿瘤组织中MSCs的研究,有望深入了解肿瘤侵袭、转移发生的机制,从而为妇科肿瘤的治疗提供新的理论依据和临床靶点。
[Abstract]:Objective to summarize the progress of mesenchymal stem cells (MSCs) in gynecological neoplasms.Methods the full text database of PubMed and CNKI journals was used to search the literature of "cervix neoplasms, ovarian tumors, uterine body tumors, vulvar tumors, vaginal tumors, tubal tumors and mesenchymal stem cells".MSCs from normal tissue and tumour 3) MSCs4) from gynecological neoplasms.According to the inclusion of the standard coincidence analysis of 29 articles.Results 1)MSCs is a kind of non-hematopoietic adult stem cells, which can differentiate into bone, cartilage and adipocytes. MSCs can regulate tumor growth.The inhibition or promotion is related to host immune function, tumor cell type and microenvironment.Tumor-related inflammatory environment can change the function of normal MSCs and make it gain the ability to recruit inflammatory mononuclear and macrophage efficiently, so as to promote the growth of tumor. MSCs can differentiate into fibroblasts.Providing structural and functional support for tumor progression, forming vascular cells, promoting microvascular formation, forming mesenchymal network to improve tumor microenvironment, thus promoting tumor proliferation. 3) MSCs also exist in tumor tissues and play an important role in the regulation of tumor proliferation.Isolation and validation from solid tumors such as lung cancer, gastric cancer and osteosarcoma. 4) MSCs with multiple differentiation potential can be isolated from cervical cancer, ovarian cancer and endometrial carcinoma from common gynecologic malignancies.The MSCs subsets of cervical cancer tissues were similar to fibroblasts and proliferated like clones. The immunophenotypes were CD13, CD29, CD4, CD4, CD105 and HLA-I, and the cells remained normal karyotype. Under suitable induction conditions, these cells could differentiate into osteoblasts and so on.Cervical cancer associated MSCs can promote the proliferation of tumor cells, the mechanism is related to angiogenesis and epithelial mesenchymal transformation.MSCswere isolated from ascites and tumor tissues of ovarian cancer. They were highly expressed CD44mMP9 and Oct4. they had normal morphology and karyotype, and could differentiate into fat, cartilage and bone. They had no tumorigenicity and could promote the growth of tumor by increasing the number of tumor stem cells.MSCs in endometrial stroma can proliferate for a long time and has the ability to differentiate and clone.The ability of MSCs invasion and invasion of ectopic endometrium is stronger.The lateral group cells isolated from endometrial carcinoma can differentiate into MSCs, form large invasive tumors in nude mice, have abundant extracellular matrix, tumor cells and interstitial cell-like cells.However, there are few reports on the regulation of endometrial cancer cell proliferation by MSCs associated with endometrial carcinoma.Conclusion through the study of MSCs in gynecological tumor tissue, it is hopeful to deeply understand the mechanism of tumor invasion and metastasis, so as to provide a new theoretical basis and clinical target for the treatment of gynecological tumor.
【作者单位】：山东省肿瘤医院妇瘤科;
【基金】：山东省自然科学基金(2009ZRC03139) 山东省医学科学院青年基金(2012-19) 山东省肿瘤医院科研启动基金(2013-13)
【分类号】：R737.3

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