Expression of the Chemokine CXCL12 and its Receptors CXCR4 and CXCR7 in Human and Nonhuman Primate Uterine Leiomyomas

Abstract

Uterine leiomyomas (also known as fibroids) are associated with several symptoms, including abnormal uterine bleeding, pressure-related symptoms, and recurrent pregnancy loss. These tumors affect up to 80% of fertile women between the ages of 30 and 50 years. However, there are currently no proven medical therapies for the long-term treatment of leiomyomas, and surgical treatment comes at a significant physical, psychological, and heath care costs. It is estimated the health system sustains annual costs of 22 billion dollars. CXCL12 (formerly known as stromal derived factor (SDF-1)) acts via its receptors CXCR4 and CXCR7 and is a potent chemokine found to be accessibly expressed in inflammatory diseases. Leiomyomas represent an inflammatory milieu; thus, we posit that the CXCL12/CXCR4/CXCR7 axis is involved in the progression of leiomyomas. This study is a prerequisite for nonhormonal and non-surgical treatment of leiomyomas. When comparing the expression of these molecules in leiomyomas vs. normal myometrium we noted the expression of this axis is elevated in humans and nonhuman primates. The similarities among human and nonhuman primates displayed extensive similarities. While CXCR4 stained both nuclei and cytoplasm in leiomyomas, CXCL12 and CXCR7 were confined to the cell membrane and cytoplasm.