Establishment of a mouse model of human uterine leiomyomata and evaluation of the presence of stem cell-like cells

Abstract

Uterine fibroids are the most common uterine tumors in women in their reproductive age. Besides clinical observations most in vivo data has been achieved from animal models like the Eker-rat whose tumors exhibit a rather sarcoma-like phenotype. Here, the design of an animal model which closely mimics uterine fibroids was addressed. By the use of tumor-derived primary cells it was possible to produce xenografts with high similarity to uterine fibroids. In the second part, we showed by fluorescence assisted cell sorting that a higher number of CD24-positive cells are present in fibroids. CD24 is mostly expressed on immature or progenitor-like cells; likewise CD24-positive fibroid cells showed similar properties. Gene expression analysis using 26 uterine fibroids with either MED12 mutation or HMGA2 rearrangements revealed that CD24 was highly expressed in both subgroups thus considering a common route of myomagenesis likely involving CD24-positive cells. It can be hypothesized that mutational changes in both genes will impact the delicate balance of uterine stem cells leading to impaired differentiation of CD24-positive cells towards CD24-negative