Volume 7, Issue 3, May 2019, Page: 92-99
A New Function of Granulocyte Colony-stimulating Factor (G-CSF): Suppression of Cell Proliferation in Uterine Endometrial Carcinoma
Yayoi Fukuda, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
Hitomi Nakamura, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
Keiichi Kumasawa, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
Tadashi Kimura, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
Received: Mar. 27, 2019;       Accepted: May 11, 2019;       Published: Jun. 12, 2019
DOI: 10.11648/j.jgo.20190703.17      View  127      Downloads  19
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.
Keywords
Granulocyte Colony-stimulating Factor (G-CSF), Uterine Endometrial Carcinoma, Assisted Reproductive Technology (ART) Treatment
To cite this article
Yayoi Fukuda, Hitomi Nakamura, Keiichi Kumasawa, Tadashi Kimura, A New Function of Granulocyte Colony-stimulating Factor (G-CSF): Suppression of Cell Proliferation in Uterine Endometrial Carcinoma, Journal of Gynecology and Obstetrics. Vol. 7, No. 3, 2019, pp. 92-99. doi: 10.11648/j.jgo.20190703.17
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Metcalf, D. (1985). The granulocyte-macrophage colony-stimulating factors. Science 229, 16-22.
[2]
Nagata, S. et al. (1986). Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319, 415-8.
[3]
Souza, L. M. et al. (1986). Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 232, 61-5.
[4]
Salmassi, A., Schmutzler, A. G., Schaefer, S., Koch, K., Hedderich, J., Jonat, W. and Mettler, L. (2005). Is granulocyte colony-stimulating factor level predictive for human IVF outcome? Hum Reprod 20, 2434-40.
[5]
ASRM@asrm.org, P.C.o.t.A.S.f.R.M.E.a. and Medicine, P.C.o.t.A.S.f.R. (2018). The role of immunotherapy in in vitro fertilization: a guideline. Fertil Steril 110, 387-400.
[6]
Freedman, M. H. et al. (2000). Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. Blood 96, 429-36.
[7]
Würfel, W. (2015). Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. J Reprod Immunol 108, 123-35.
[8]
Klocke, R., Kuhlmann, M. T., Scobioala, S., Schäbitz, W. R. and Nikol, S. (2008). Granulocyte colony-stimulating factor (G-CSF) for cardio- and cerebrovascular regenerative applications. Curr Med Chem 15, 968-77.
[9]
Wang, J. et al. (2012). Granulocyte-colony stimulating factor promotes proliferation, migration and invasion in glioma cells. Cancer Biol Ther 13, 389-400.
[10]
Chakraborty, A. and Guha, S. (2007). Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of bladder cancer cells. Urology 69, 1210-5.
[11]
Moon, H. W., Kim, T. Y., Oh, B. R., Hwang, S. M., Kwon, J., Ku, J. L. and Lee, D. S. (2012). Effects of granulocyte-colony stimulating factor and the expression of its receptor on various malignant cells. Korean J Hematol 47, 219-24.
[12]
Duan, J. S. (1990). Production of granulocyte colony stimulating factor in decidual tissue and its significance in pregnancy. Osaka City Med J 36, 81-97.
[13]
Vandermolen, D. T. and Gu, Y. (1996). Human endometrial expression of granulocyte colony-stimulating factor (G-CSF) and its receptor, stimulation of endometrial G-CSF production by interleukin-1 beta, and G-CSF inhibition of choriocarcinoma cell proliferation. Am J Reprod Immunol 36, 278-84.
[14]
Marino, V. J. and Roguin, L. P. (2008). The granulocyte colony stimulating factor (G-CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line. J Cell Biochem 103, 1512-23.
[15]
Zhao, J., Tian, T., Zhang, Q., Wang, Y. and Li, Y. (2013). Use of granulocyte colony-stimulating factor for the treatment of thin endometrium in experimental rats. PLoS One 8, e82375.
[16]
Gessler, P., Neu, S., Brockmann, Y. and Speer, C. P. (2000). Decreased mRNA expression of G-CSF receptor in cord blood neutrophils of term newborns: regulation of expression by G-CSF and TNF-alpha. Biol Neonate 77, 168-73.
[17]
Zada, A. A. et al. (2006). Proteomic discovery of Max as a novel interacting partner of C/EBPalpha: a Myc/Max/Mad link. Leukemia 20, 2137-46.
[18]
Slayton, W. B., Juul, S. E., Calhoun, D. A., Li, Y., Braylan, R. C. and Christensen, R. D. (1998). Hematopoiesis in the liver and marrow of human fetuses at 5 to 16 weeks postconception: quantitative assessment of macrophage and neutrophil populations. Pediatr Res 43, 774-82.
[19]
Bonello, N., Jasper, M. J. and Norman, R. J. (2004). Periovulatory expression of intercellular adhesion molecule-1 in the rat ovary. Biol Reprod 71, 1384-90.
[20]
Kendrick, T. S. and Bogoyevitch, M. A. (2007). Activation of mitogen-activated protein kinase pathways by the granulocyte colony-stimulating factor receptor: mechanisms and functional consequences. Front Biosci 12, 591-607.
[21]
Layton, J. E. and Hall, N. E. (2006). The interaction of G-CSF with its receptor. Front Biosci 11, 3181-9.
[22]
Hörtner, M., Nielsch, U., Mayr, L. M., Johnston, J. A., Heinrich, P. C. and Haan, S. (2002). Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction. J Immunol 169, 1219-27.
[23]
Migliaccio, A. et al. (1998). Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor. EMBO J 17, 2008-18.
[24]
Boonyaratanakornkit, V., Scott, M. P., Ribon, V., Sherman, L., Anderson, S. M., Maller, J. L., Miller, W. T. and Edwards, D. P. (2001). Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol Cell 8, 269-80.
[25]
Cha, J., Sun, X. and Dey, S. K. (2012). Mechanisms of implantation: strategies for successful pregnancy. Nat Med 18, 1754-67.
[26]
Colombo, N. et al. (2016). ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol 27, 16-41.
[27]
El-Toukhy, T., Coomarasamy, A., Khairy, M., Sunkara, K., Seed, P., Khalaf, Y. and Braude, P. (2008). The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril 89, 832-9.
[28]
Weissman, A., Gotlieb, L. and Casper, R. F. (1999). The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in an in vitro fertilization program. Fertil Steril 71, 147-9.
[29]
Gleicher, N., Kim, A., Michaeli, T., Lee, H. J., Shohat-Tal, A., Lazzaroni, E. and Barad, D. H. (2013). A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum Reprod 28, 172-7.
[30]
Barad, D. H., Yu, Y., Kushnir, V. A., Shohat-Tal, A., Lazzaroni, E., Lee, H. J. and Gleicher, N. (2014). A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates. Fertil Steril 101, 710-5.
[31]
Kim, J. J., Kurita, T. and Bulun, S. E. (2013). Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev 34, 130-62.
[32]
Tanaka, T. and Umesaki, N. (2003). Regulation of the cellular subpopulation ratios of normal human endometrial stromal cells by macrophage colony-stimulating factor. Int J Mol Med 11, 617-20.
Browse journals by subject