Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
Reprod Sci. 2020 Sep;27(9):1724-1730. doi: 10.1007/s43032-020-00166-x. Epub 2020 Feb 4.
Uterine leiomyomas, also known as fibroids or myomas, are a common benign gynecologic tumor found in women of reproductive age. Though advances have been made in understanding leiomyomas, the etiology and pathogenesis of this disease are not fully characterized. Current evidence supports a role of putative human uterine stem/progenitor cells in the onset of uterine disease such as uterine myomas. In this study, we report that increased expression of CXCL12 in leiomyomas recruits bone marrow-derived cells (BMDCs) that may contribute to leiomyoma growth. Tissue was collected from leiomyomas or control myometrium from women with or without leiomyomas. qRT-PCR analysis showed increased expression of CXCL12 and decreased CXCR4 expression in the leiomyoma and myometrium of women with leiomyoma compared with normal myometrium. Increased CXCL12 protein secretion from cultured myoma cells was confirmed by ELISA. Further, we found that BMDCs migration was increased toward leiomyoma conditioned medium compared with conditioned medium from normal myometrium. CXCR4 antagonist AMD3100 completely blocked this migration. Engraftment of BMDCs significantly increased in myoma of mouse uteri treated with CXCL12 compared with placebo. We conclude that CXCL12 may play a role in leiomyomas growth by attracting bone marrow-derived cells to leiomyoma. Therefore, CXCL12 and its receptors are novel targets for leiomyoma therapy.
子宫平滑肌瘤，也称为纤维瘤或肌瘤，是一种常见的良性妇科肿瘤，发生在育龄妇女中。尽管在理解平滑肌瘤方面取得了进展，但这种疾病的病因和发病机制尚未完全阐明。目前的证据支持人子宫干/祖细胞在子宫疾病（如子宫肌瘤）发病中的作用。在这项研究中，我们报告称，CXCL12 的表达增加会招募骨髓来源的细胞（BMDCs），这些细胞可能有助于子宫肌瘤的生长。从有或没有子宫肌瘤的妇女的子宫肌瘤或对照子宫肌中收集组织。qRT-PCR 分析显示，与正常子宫肌相比，患有子宫肌瘤的妇女的肌瘤和子宫肌中 CXCL12 的表达增加，而 CXCR4 的表达减少。ELISA 证实培养的肌瘤细胞中 CXCL12 蛋白分泌增加。此外，我们发现与正常子宫肌的条件培养基相比，BMDCs 向子宫肌瘤条件培养基的迁移增加。CXCR4 拮抗剂 AMD3100 完全阻断了这种迁移。与安慰剂相比，用 CXCL12 处理的小鼠子宫肌瘤中的 BMDCs 明显增加。我们得出结论，CXCL12 可能通过吸引骨髓来源的细胞到子宫肌瘤中来发挥作用。因此，CXCL12 及其受体是子宫肌瘤治疗的新靶点。
