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CXCL12 Attracts Bone Marrow-Derived Cells to Uterine Leiomyomas.

Authors
  • Moridi, Irene1
  • Mamillapalli, Ramanaiah2
  • Kodaman, Pinar H1
  • Habata, Shutaro1
  • Dang, Tran1
  • Taylor, Hugh S1
  • 1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
  • 2 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA. [email protected]
Type
Published Article
Journal
Reproductive Sciences
Publisher
SAGE Publications
Publication Date
Sep 01, 2020
Volume
27
Issue
9
Pages
1724–1730
Identifiers
DOI: 10.1007/s43032-020-00166-x
PMID: 32020550
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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