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.
Highlights
Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is named after its ability to induce the proliferation and differentiation of neutrophil precursors
G-CSF receptor (G-CSF-R) mRNA-expression levels were analyzed in HEC-1-A and Ishikawa human uterine endometrial carcinoma cells (Figure 1)
We showed that G-CSF dose-dependently suppressed cell proliferation, independently of G-CSF-R
Summary
Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is named after its ability to induce the proliferation and differentiation of neutrophil precursors. G-CSF has been used worldwide for treating patients with neutropenia for over 2 decades. G-CSF has long been studied for its effects on hematopoietic cells and for its role in female reproduction. Among patients in assisted reproductive technology (ART) treatment, who received fresh embryo transfers, the pregnant women showed significantly higher serum G-CSF levels than those in the non-pregnant group [4]. It has been considered that G-CSF might be able to promote uterine endometrium proliferation and help in preparation for implantation. To improve the implantation rate, several clinical trials were conducted wherein G-CSF was administered by local uterine injection or subcutaneous injection in patients who received embryo transfers [5].
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