Uterine leiomyomas exhibit fewer stem/progenitor cell characteristics when compared with corresponding normal myometrium.
Uterine leiomyomas exhibit fewer stem/progenitor cell characteristics when compared with corresponding normal myometrium.
复制标题
DOI：
10.1177/1933719109348924
复制
发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Teixeira J
中科院分区：
文献类型：
--
作者：
Chang HL;Senaratne TN;Zhang L;Szotek PP;Stewart E;Dombkowski D;Preffer F;Donahoe PK;Teixeira J
子宫肌瘤（也称为子宫肌瘤）是女性生殖道最常见的良性肿瘤，也是子宫切除术最常见的单一适应症。尽管它们的患病率很高，但这些良性肿瘤的确切发病机制仍然未知。平滑肌瘤形成的一种可能机制是间充质干细胞活性失调。已在人类和小鼠子宫中鉴定出间充质干细胞，并在女性生殖恶性肿瘤中鉴定出癌症干细胞。我们比较了正常子宫肌层和接受子宫切除术的患者相应的平滑肌瘤的干/祖细胞特征。我们发现，与从正常子宫肌层分离的细胞相比，平滑肌瘤细胞形成较少的间充质干细胞集落，并且表现出较少的排除赫斯特染料的侧群活性，这是与其他组织中的祖细胞相关的功能。在正常子宫肌层中，我们观察到 CD90 的异质表达，CD90 是一种与子宫成纤维细胞分化潜能相关的细胞表面标记物，而在平滑肌瘤中，我们观察到 CD90 的同质表达，表明平滑肌瘤细胞的终末分化程度更高。此外，我们发现虽然平滑肌瘤细胞只能产生表达CD90的细胞，但CD90+和CD90−子宫肌层细胞在体外扩增时都可以重建其原始的异质CD90谱。这些结果表明，正常子宫肌层含有具有平滑肌瘤中不存在的干/祖细胞活性的细胞。
Uterine leiomyomas (also known as uterine fibroids) are the most common benign tumors of female reproductive tract and are the single most common indication for hysterectomies. Despite their high prevalence, the exact pathogenesis of these benign tumors is still unknown. One possible mechanism for leiomyoma formation is dysregulation of mesenchymal stem cell activity. Mesenchymal stem cells have been identified in both human and murine uteri and cancer stem cells have been identified in female reproductive malignancies. We compared stem/progenitor cell characteristics in both normal myometrium and the corresponding leiomyoma of patient’s undergoing hysterectomies. We found that leiomyoma cells form fewer mesenchymal stem cell colonies and exhibit less Hoechst dye-excluding side population activity, which is a function associated with progenitor cells in other tissues, than cells isolated from normal myometrium. Whereas in normal myometrium we observed heterogeneous expression of CD90, a cell surface marker associated the with differentiation potential of uterine fibroblasts, in leiomyomas, we observed homogenous expression of CD90, suggesting leiomyoma cells are more terminally differentiated. Furthermore, we found that while leiomyoma cells could only produce CD90 expressing cells, both CD90+ and CD90− myometrial cells could reestablish their original heterogeneous CD90 profile when expanded in vitro. These results suggest that normal myometrium contains cells with stem/progenitor cell activities that are absent in leiomyomas.
登录
查看更多内容
DOI：
10.1073/pnas.89.7.2804
发表时间：
1992-04-01
影响因子：
11.1
作者：
BAUM, CM;WEISSMAN, IL;PEAULT, B
通讯作者：
PEAULT, B
影响因子：
2.9
作者：
Kayisli, Umit A.;Berkkanoglu, Murat;Arici, Aydin
通讯作者：
Arici, Aydin
影响因子：
6
作者：
Koumas, L;King, AE;Phipps, RP
通讯作者：
Phipps, RP
影响因子：
3.5
作者：
Dixon, D;Flake, GP;Robboy, SJ
通讯作者：
Robboy, SJ
影响因子：
6.1
作者：
Kato, Kiyoko;Yoshimoto, Momoko;Wake, Norio
通讯作者：
Wake, Norio