A New Function of Granulocyte Colony-stimulating Factor (G-CSF): Suppression of Cell Proliferation in Uterine Endometrial Carcinoma

Abstract

Granulocyte colony-stimulating factor (G-CSF) is cytokine which belongs to the family of colony-stimulating factors and recombinant human G-CSF has been widely used in clinical practice for treating patients with neutropenia for over 20 years. Recently, it has also seen use in assisted reproductive technology (ART) treatment based on the hypothesis that G-CSF might help the uterine endometrium proliferate and prepare for implantation. However, the risk of this treatment has not been fully assessed yet and there is a potential complication with its usage. It has been reported that G-CSF stimulates cell proliferation in hematopoietic cells and various other cell types, including cancer cells, suggesting that repeated local G-CSF administration into the uterine cavity might raises the risk of contracting uterine endometrial carcinoma. Based on this hypothesis, we assessed the effect of G-CSF on human uterine carcinoma cell proliferation, using cell lines. Our study showed that G-CSF administration produced dose-dependent suppression of proliferation of human uterine endometrial carcinoma cells through a G-CSF receptor-independent mechanism via a part of mitogen-activated protein kinase (MAPK) signaling pathway. While further studies will be needed to confirm G-CSFs efficacy in improving the outcomes of ART treatment, our data at least suggests that repeated G-CSF administration does not increase the risk of uterine endometrial carcinoma and may even lower it.