Paracrine Pathways in Uterine Leiomyoma Stem Cells Involve Insulinlike Growth Factor 2 and Insulin Receptor A.

Context: Uterine leiomyomas (fibroids) are the most common benign tumors in women. Recently, three populations of leiomyoma cells were discovered on the basis of CD34 and CD49b expression, but molecular differences between these populations remain unknown.

Objective: To define differential gene expression and signaling pathways in leiomyoma cell populations.

Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

Study Question: Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model?

Summary Answer: HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis.

What Is Known Already: Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro.

Human uterine leiomyoma stem/progenitor cells expressing CD34 and CD49b initiate tumors in vivo.

Context: Uterine leiomyoma is the most common benign tumor in reproductive-age women. Using a dye-exclusion technique, we previously identified a side population of leiomyoma cells exhibiting stem cell characteristics. However, unless mixed with mature myometrial cells, these leiomyoma side population cells did not survive or grow well in vitro or in vivo.

Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth.

Objective: To assess the effect of three WNT/β-catenin pathway inhibitors-inhibitor of β-catenin and TCF4 (ICAT), niclosamide, and XAV939-on the proliferation of primary cultures of human uterine leiomyoma cells.

Design: Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.

Setting: University research laboratory.

Down-regulation of miR-29b is essential for pathogenesis of uterine leiomyoma.

Uterine leiomyomata (LMs) are the most common tumor affecting the female reproductive organs. The most notable pathophysiologic feature of this tumor is the excessive accumulation of rigid extracellular matrix (ECM) composed mainly of collagen types I and III. It is believed that the rigidity of the collagen-rich ECM causes symptoms such as abnormal bleeding and pelvic pain/pressure.

Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth.

Uterine leiomyomas are extremely common estrogen and progesterone-dependent tumors of the myometrium and cause irregular uterine bleeding, severe anemia, and recurrent pregnancy loss in 15-30% of reproductive-age women. Each leiomyoma is thought to arise from a single mutated myometrial smooth muscle stem cell. Leiomyoma side-population (LMSP) cells comprising 1% of all tumor cells and displaying tumor-initiating stem cell characteristics are essential for estrogen- and progesterone-dependent in vivo growth of tumors, although they have remarkably lower estrogen/progesterone receptor levels than mature myometrial or leiomyoma cells.