Targeting Tumor Initiating Cells in Human Uterine Leiomyma with an Anti-RANKL Antibody to Reduce or Prevent Fibroid Growth

In uterine fibroids, progesterone stimulates RANKL expression in intermediate-stage CD34+CD49b- cells which then acts in a paracrine manner to activate RANK on CD34+CD49b- TICs, thereby stimulating tumor cell proliferation. Blocking the RANKL/RANK paracrine signaling pathway with an anti-RANKL antibody will reduce fibroid tumor size in an animal model. Our overall goal is to characterize the paracrine activation and expansion of leiomyoma TICs by progesterone via the RANKL/RANK pathway and determine whether antibody-based interference of this pathway prevents TIC expansion and fibroid growth. To achieve this goal, we propose to evaluate the paracrine stimulatory function of CD34+CD49b- cells on the proliferation of CD34+ CD49b+ cells.