Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth

Serdar E. Bulun, Molly B. Moravek, Ping Yin, Masanori Ono, John S. Coon V, Matthew T. Dyson, Antonia Navarro, Erica E. Marsh, Hong Zhao, Tetsuo Maruyama, Debabrata Chakravarti, J. Julie Kim, Jian Jun Wei

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Uterine leiomyomas (fibroids) represent the most common class of benign tumors in women. Multiple leiomyomas usually arise from the uterus of a symptomatic woman. These tumors cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are responsible for more than 200,000 hysterectomies in the United States annually. Each leiomyoma seems to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a mutation. Tumor expansion is sustained by cell proliferation together with the production of large amounts of extracellular matrix. Estrogen and progesterone stimulate the growth of leiomyomas. Estrogen, together with its receptor ERα, enables progesterone action via induction of progesterone receptor (PR) expression. Progesterone induces the growth of leiomyoma by regulation of a set of key genes that control proliferation and apoptosis. A distinct cell population with stem-progenitor properties is indispensable for progesterone-dependent growth of leiomyomas. This stem-progenitor cell population is deficient in ERα and PR and dependent on the much higher levels of these steroid receptors in surrounding mature leiomyoma or myometrial cells. Progesterone sends paracrine signals from these mature cells to stem cells. The WNT/β-catenin pathway comprises a key component of this paracrine signaling system. The majority of medical treatments currently available for leiomyoma works by inhibiting estrogen or progesterone production or action, but tumors tend to regrow once treatment is stopped. Targeting stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma may lead to the development of more effective therapeutics.

Original languageEnglish
Pages (from-to)357-365
Number of pages9
JournalSeminars in Reproductive Medicine
Volume33
Issue number5
DOIs
Publication statusPublished - 2015 Aug 6

Fingerprint

Leiomyoma
Progesterone
Stem Cells
Growth
Estrogens
Progesterone Receptors
Neoplasms
Paracrine Communication
Population
Catenins
Pelvic Pain
Uterine Hemorrhage
Steroid Receptors
Hysterectomy
Uterus
Smooth Muscle Myocytes
Extracellular Matrix
Urinary Bladder
Therapeutics
Cell Proliferation

Keywords

  • estrogen
  • fibroid
  • leiomyoma
  • progesterone
  • stem cells

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Bulun, S. E., Moravek, M. B., Yin, P., Ono, M., Coon V, J. S., Dyson, M. T., ... Wei, J. J. (2015). Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth. Seminars in Reproductive Medicine, 33(5), 357-365. https://doi.org/10.1055/s-0035-1558451

Uterine Leiomyoma Stem Cells : Linking Progesterone to Growth. / Bulun, Serdar E.; Moravek, Molly B.; Yin, Ping; Ono, Masanori; Coon V, John S.; Dyson, Matthew T.; Navarro, Antonia; Marsh, Erica E.; Zhao, Hong; Maruyama, Tetsuo; Chakravarti, Debabrata; Kim, J. Julie; Wei, Jian Jun.

In: Seminars in Reproductive Medicine, Vol. 33, No. 5, 06.08.2015, p. 357-365.

Research output: Contribution to journalArticle

Bulun, SE, Moravek, MB, Yin, P, Ono, M, Coon V, JS, Dyson, MT, Navarro, A, Marsh, EE, Zhao, H, Maruyama, T, Chakravarti, D, Kim, JJ & Wei, JJ 2015, 'Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth', Seminars in Reproductive Medicine, vol. 33, no. 5, pp. 357-365. https://doi.org/10.1055/s-0035-1558451
Bulun SE, Moravek MB, Yin P, Ono M, Coon V JS, Dyson MT et al. Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth. Seminars in Reproductive Medicine. 2015 Aug 6;33(5):357-365. https://doi.org/10.1055/s-0035-1558451
Bulun, Serdar E. ; Moravek, Molly B. ; Yin, Ping ; Ono, Masanori ; Coon V, John S. ; Dyson, Matthew T. ; Navarro, Antonia ; Marsh, Erica E. ; Zhao, Hong ; Maruyama, Tetsuo ; Chakravarti, Debabrata ; Kim, J. Julie ; Wei, Jian Jun. / Uterine Leiomyoma Stem Cells : Linking Progesterone to Growth. In: Seminars in Reproductive Medicine. 2015 ; Vol. 33, No. 5. pp. 357-365.
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