Abstract
Melanogenic paracrine and autocrine cytokine networks have recently been discovered in vitro between melanocytes and other types of skin cells. Granulocyte colony-stimulating factor receptor (CSF3R) controls the survival, proliferation and differentiation of many kinds of cells, including neutrophils. To understand the function of CSF3R and recombinant human granulocyte colony-stimulating factor (rhCSF3) on melanocyte proliferation, this study compared the expression of CSF3R and the effects of rhCSF3 in primary human melanocytes, neutrophils and HEL 92.1.7 cells. The results show that CSF3R is localized in the cytoplasm and on cell membranes of melanocytes and neutrophils. The percentage of CSF3R+ melanocytes was higher than CSF3R+ HEL 92.1.7 cells, but was lower than CSF3R+ neutrophils. Both CSF3R mRNA and CSF3R protein levels in melanocytes were higher than in HEL 92.1.7 cells, but were lower than in neutrophils. Treatment with rhCSF3 increased the proliferation of human melanocytes, but not their tyrosinase activity. Transcripts of CSF3R in human melanocytes, M14, A375 melanoma and A431 squamous cell carcinoma cells were also detected. Expression of the CSF3R V3 transcript was lower in melanocytes than in M14, A375 melanoma and A431 squamous cell carcinoma cells. In conclusion, rhCSF3 can promote melanocyte proliferation through CSF3R without affecting tyrosinase activity.
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Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C, European Organisation for Research and Treatment of Cancer (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47:8–32
Avalos BR (1996) Molecular analysis of the granulocyte colony-stimulating factor receptor. Blood 88:761–777
Basu S, Dunn A, Ward A (2002) G-CSF: function and modes of action (Review). Int J Mol Med 10:3–10
Bennett CL, Djulbegovic B, Norris LB, Armitage JO (2013) Colony-stimulating factors for febrile neutropenia during cancer therapy. N Engl J Med 368:1131–1139
Bernard T, Gale RE, Linch DC (1996) Analysis of granulocyte colony stimulating factor receptor isoforms, polymorphisms and mutations in normal haemopoietic cells and acute myeloid leukaemia blasts. Br J Haematol 93:527–533
Cook PW, Pittelkow MR, Shipley GD (1991) Growth factor-independent proliferation of normal human neonatal keratinocytes: production of autocrine- and paracrine-acting mitogenic factors. J Cell Physiol 146:277–289
de Koning JP, Schelen AM, Dong F, van Buitenen C, Burgering BM, Bos JL, Löwenberg B, Touw IP (1996) Specific involvement of tyrosine of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes. Blood 87:132–140
Di Gregoli K, Johnson JL (2012) Role of colony-stimulating factors in atherosclerosis. Curr Opin Lipidol 23:412–421
Dong F, van Buitenen C, Pouwels K, Hoefsloot LH, Löwenberg B, Touw IP (1993) Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol Cell Biol 13:7774–7781
Dong F, van Paassen M, van Buitenen C, Hoefsloot LH, Löwenberg B, Touw IP (1995) A point mutation in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene in a case of acute myeloid leukemia results in the overexpression of a novel G-CSF-R isoform. Blood 85:902–911
Fukunaga R, Seto Y, Mizushima S, Nagata S (1990) Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci USA 87:8702–8706
Gyanchandani R, Sano D, Ortega Alves MV, Klein JD, Knapick BA, Oh S, Myers JN, Kim S (2013) Interleukin-8 as a modulator of response to bevacizumab in preclinical models of head and neck squamous cell carcinoma. Oral Oncol 49:761–770
Hirobe T (2011) How are proliferation and differentiation of melanocytes regulated? Pigment Cell Melanoma Res 24:462–478
Hirobe T, Osawa M, Nishikawa S (2004) Hepatocyte growth factor controls the proliferation of cultured epidermal melanoblasts and melanocytes from newborn mice. Pigment Cell Res 17:51–61
Hirobe T, Shinpo T, Higuchi K, Sano T (2010) Life cycle of human melanocytes is regulated by endothelin-1 and stem cell factor in synergy with cyclic AMP and basic fibroblast growth factor. J Dermatol Sci 57:123–131
Hollenstein U, Homoncik M, Stohlawetz PJ, Marsik C, Sieder A, Eichler HG, Jilma B (2000) Endotoxin down-modulates granulocyte colony-stimulating factor receptor (CD114) on human neutrophils. J Infect Dis 182:343–346
Jung GD, Yang JY, Song ES, Par JW (2005) Stimulation of melanogenesis by glycyrrhizin in B16 melanoma cells. Exp Mol Med 33:131–135
Khera S, Tiwari A, Srinivasan R, Gupta A, Luthra-Guptasarma M (2011) Expression of granulocyte colony stimulating factor and its receptor by retinal pigment epithelial cells: a role in maintaining differentiation-competent state. Curr Eye Res 36:469–480
Lei TC, Virador VM, Vieira WD, Hearing VJ (2002) A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. Anal Biochem 305:260–268
Lu Y, Zhu WY, Tan C, Yu GH, Gu JX (2002) Melanocytes are potential immunocompetent cells: evidence from recognition of immunological characteristics of cultured human melanocytes. Pigment Cell Res 15:454–460
Liu F, Poursine-Laurent J, Link DC (2000) Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood 95:3025–3031
Marino VJ, Roguin LP (2008) The granulocyte colony stimulating factor (G-CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line. J Cell Biochem 103:1512–1523
Ringden OTH, Le Blanc K, Remberger M (2005) Granulocyte and granulocyte-macrophage colony-stimulating factors in allografts: uses, misuses, misconceptions, and future applications. Exp Hematol 33:505–512
Slominski A, Tobin DJ, Shibahara S, Wortsman J (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84:1155–1228
Slominski A, Wortsman J (2000) Neuroendocrinology of the skin. Endocr Rev 21:457–487
Slominski A, Zmijewski MA, Pawelek J (2012) l-tyrosine and l-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment Cell Melanoma Res 25:14–27
Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD (2012) Sensing the environment: regulation of local and global homeostasis by the skin’s neuroendocrine system. Adv Anat Embryol Cell Biol 212:v (vii, 1–115)
Slominski AT, Zmijewski MA, Zbytek B, Tobin DJ, Theoharides TC, Rivier J (2013) Key role of CRF in the skin stress response system. Endocr Rev 34:827–884
Swope VB, Medrano EE, Smalara D, Abdel-Malek ZA (1995) Long-term pro1iferation of human melanocytes is supported by the physiologic mitogens alpha-melanotropin, endothelin-l, and basic fibroblast growth factor. Exp Cell Res 217:453–459
Tweardy DJ, Anderson K, Cannizzaro LA, Steinman RA, Croce CM, Huebner K (1992) Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor receptor from HL-60 and mapping of the gene to chromosome region 1p32-34. Blood 79:1148–1154
Yang X, Liu F, Xu Z, Chen C, Wu X, Li G, Li J (2005) Expression of granulocyte colony stimulating factor receptor in human colorectal cancer. Postgrad Med J 81:333–337
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This study was supported by the National Natural Science Foundation of China (Grant NO.81171517).
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Y. Lu and Z. Guo equally contributed to this manuscript and should be considered co-first authors.
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Lu, Y., Guo, Z., Zhou, MH. et al. rhCSF3 accelerates the proliferation of human melanocytes in culture through binding CSF3R and the expression of CSF3R transcripts. Arch Dermatol Res 307, 341–350 (2015). https://doi.org/10.1007/s00403-015-1545-3
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DOI: https://doi.org/10.1007/s00403-015-1545-3