Does vascular endothelial growth factor participate in uterine myoma growth stimulation?

Abstract

Peptide growth factors play a role in the rebuilding of extracellular matrix in the course of leiomyoma growth, and exert a regulative effect on the cell only when they bind with a specific membrane receptor and transmit a signal into the cell. A high content of certain peptide growth factors and their receptors in leiomyoma suggests that in the course of the tumour growth hyperstimulation of cells takes place. A combined action of various peptide growth factors causes an amplification of signal paths in cells, inducing gene expression of proteins responsible for cell division and changes of metabolism. We therefore decided to evaluate the amounts and expression of VEGF, their receptor and mRNA levels. Studies were performed on human myometrium and uterine leiomyomas of various weights (small: i.e. less than 10 g, and large: i.e. more than 100 g). Expression and content of VEGF-A, D and VEGF R-1, R-2 were analysed with Western blot and ELISA methods, respectively. The RT-PCR method was used to determine VEGF mRNA levels. Our immunoblotting studies and immunoenzymatic assay, as well as RT-PCR technique, did not detect significant differences in the expression of VEGFs and their receptors in control myometrium and in uterine leiomyomas. The increase in the amount of some peptide growth factors, especially FGFs and IGF-I, in large leiomyomas without any change in VEGF content means a decrease in the proportional relationship of the latter to other growth factors. Stimulation of extracellular matrix formation seems stronger than angiogenesis during myoma growth.