CXCL12 Attracts Bone Marrow-Derived Cells to Uterine Leiomyomas.
CXCL12 Attracts Bone Marrow-Derived Cells to Uterine Leiomyomas.
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CXCL12 将骨髓来源的细胞吸引至子宫平滑肌瘤。
DOI：
10.1007/s43032-020-00166-x
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Taylor,HughS
中科院分区：
文献类型：
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作者：
Moridi,Irene;Mamillapalli,Ramanaiah;Kodaman,PinarH;Habata,Shutaro;Dang,Tran;Taylor,HughS
子宫平滑肌瘤，也称为肌瘤或肌瘤，是一种常见的良性妇科肿瘤，发现在育龄妇女。虽然对平滑肌瘤的认识已经取得了进展，但该病的病因和发病机制尚未完全确定。目前的证据支持假定的人子宫干/祖细胞在子宫疾病如子宫肌瘤的发病中的作用。在这项研究中，我们报告了CXCL 12在平滑肌瘤中的表达增加，招募骨髓源性细胞（BMDCs），这可能有助于平滑肌瘤的生长。组织收集自平滑肌瘤或来自患有或不患有平滑肌瘤的女性的对照子宫肌层。qRT-PCR分析显示，与正常子宫肌层相比，子宫肌瘤患者的子宫肌瘤和子宫肌层中CXCL 12表达增加，CXCR 4表达减少。通过ELISA证实培养的肌瘤细胞的CXCL 12蛋白分泌增加。此外，我们发现与来自正常子宫肌层的条件培养基相比，BMDC向平滑肌瘤条件培养基的迁移增加。CXCR 4拮抗剂AMD 3100完全阻断了这种迁移。与安慰剂相比，用CXCL 12治疗的小鼠子宫肌瘤中BMDC的移植显着增加。我们的结论是，CXCL 12可能通过吸引骨髓来源的细胞到平滑肌瘤生长中发挥作用。因此，CXCL 12及其受体是平滑肌瘤治疗的新靶点。
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.