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

Project: Research project

Description

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.
StatusFinished
Effective start/end date9/1/138/31/15

Funding

  • Northwestern Memorial Hospital (Master Agmt/9-22-13/EX-B13)

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Neoplastic Stem Cells
Leiomyoma
Anti-Idiotypic Antibodies
Growth
Progesterone
Cell Proliferation
Antibodies