LRRC33 is a novel binding and potential regulating protein of TGF-β1 function in human acute myeloid leukemia cells
Autoři:
Wenjiang Ma aff001; Yan Qin aff001; Bjoern Chapuy aff002; Chafen Lu aff001
Působiště autorů:
Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA, United States of America
aff001; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America
aff002; Harvard Medical School, Boston, MA, United States of America
aff003
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0213482
Souhrn
Transforming growth factor‑β1 (TGF-β1) is a versatile cytokine. It has context-dependent pro- and anti-cell proliferation functions. Activation of latent TGF-β1 requires release of the growth factor from pro-complexes and is regulated through TGF-β binding proteins. Two types of TGF-β binding partners, latent TGF-β-binding proteins (LTBPs) and leucine-rich-repeat-containing protein 32 (LRRC32), have been identified and their expression are cell specific. TGF-β1 also plays important roles in acute myeloid leukemia (AML) cells. However, the expression of LTBPs and LRRC32 are lacking in myeloid lineage cells and the binding protein of TGF-β1 in these cells are unknown. Here we show that a novel leucine-rich-repeat-containing protein family member, LRRC33, with high mRNA level in AML cells, to be the binding and regulating protein of TGF-β1 in AML cells. Using two representative cell lines MV4-11 and AML193, we demonstrate that the protein expression of LRRC33 and TGF-β1 are correlated. LRRC33 co-localizes and forms complex with latent TGF-β1 protein on the cell surface and intracellularly in these cells. Similar as in other cell types, the activation of TGF-β1 in MV4-11 and AML193 cells are also integrin dependent. We anticipate our study to be a starting point of more comprehensive research on LRRC33 as novel TGF-β regulating protein and potential non-genomic based drug target for AML and other myeloid malignancy.
Klíčová slova:
Acute myeloid leukemia – Cell binding – Cell staining – Flow cytometry – Immunoprecipitation – Protein complexes – TGF-beta signaling cascade – Integrins
Zdroje
1. Wu MY, Hill CS. Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev Cell. 2009;16(3):329–43. doi: 10.1016/j.devcel.2009.02.012 19289080.
2. Massagué J, Gomis RR. The logic of TGFbeta signaling. FEBS Lett. 2006;580(12):2811–20. Epub 2006/04/21. doi: 10.1016/j.febslet.2006.04.033 16678165.
3. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000;342(18):1350–8. Epub 2000/05/04. doi: 10.1056/NEJM200005043421807 10793168.
4. Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, et al. Latent TGF-β structure and activation. Nature. 2011;474(7351):343–9. Epub June 16, 2011. doi: 10.1038/nature10152 PubMed Central PMCID: PMC Journal In Process. 21677751
5. Rifkin DB. Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability. J Biol Chem. 2005;280(9):7409–12. doi: 10.1074/jbc.R400029200 15611103.
6. Kanzaki T, Olofsson A, Morén A, Wernstedt C, Hellman U, Miyazono K, et al. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell. 1990;61(6):1051–61. doi: 10.1016/0092-8674(90)90069-q 2350783.
7. Miyazono K, Hellman U, Wernstedt C, Heldin CH. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988;263(13):6407–15. 3162913.
8. Robertson IB, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K, Rifkin DB. Latent TGF-beta-binding proteins. Matrix Biol. 2015;47:44–53. doi: 10.1016/j.matbio.2015.05.005 25960419; PubMed Central PMCID: PMC4844006.
9. Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM. GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009;106(32):13445–50. Epub 2009/07/27. doi: 10.1073/pnas.0901944106 19651619; PubMed Central PMCID: PMC2726354.
10. Wang R, Kozhaya L, Mercer F, Khaitan A, Fujii H, Unutmaz D. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009;106(32):13439–44. Epub 2009/08/12. 0901965106 [pii] doi: 10.1073/pnas.0901965106 19666573; PubMed Central PMCID: PMC2726405.
11. Wang R, Zhu J, Dong X, Shi M, Lu C, Springer TA. GARP regulates the bioavailability and activation of TGF-β. Mol Biol Cell. 2012;23:1129–39. doi: 10.1091/mbc.E11-12-1018 22278742; PubMed Central PMCID: PMC3302739.
12. Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985;82(1):119–23. doi: 10.1073/pnas.82.1.119 3871521; PubMed Central PMCID: PMC396983.
13. Hu X, Zuckerman KS. Transforming growth factor: signal transduction pathways, cell cycle mediation, and effects on hematopoiesis. J Hematother Stem Cell Res. 2001;10(1):67–74. doi: 10.1089/152581601750098255 11276360.
14. Taetle R, Payne C, Dos Santos B, Russell M, Segarini P. Effects of transforming growth factor beta 1 on growth and apoptosis of human acute myelogenous leukemia cells. Cancer Res. 1993;53(14):3386–93. 8324749.
15. Taipale J, Matikainen S, Hurme M, Keski-Oja J. Induction of transforming growth factor beta 1 and its receptor expression during myeloid leukemia cell differentiation. Cell Growth Differ. 1994;5(12):1309–19. 7696179.
16. Davis MR, Andersson R, Severin J, de Hoon M, Bertin N, Baillie JK, et al. Transcriptional profiling of the human fibrillin/LTBP gene family, key regulators of mesenchymal cell functions. Mol Genet Metab. 2014;112(1):73–83. doi: 10.1016/j.ymgme.2013.12.006 24703491; PubMed Central PMCID: PMC4019825.
17. Robertson IB, Rifkin DB. Regulation of the Bioavailability of TGF-beta and TGF-beta-Related Proteins. Cold Spring Harb Perspect Biol. 2016;8(6). doi: 10.1101/cshperspect.a021907 27252363.
18. Metelli A, Wu BX, Fugle CW, Rachidi S, Sun S, Zhang Y, et al. Surface Expression of TGFbeta Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer. Cancer Res. 2016;76(24):7106–17. doi: 10.1158/0008-5472.CAN-16-1456 27913437; PubMed Central PMCID: PMC5504525.
19. Rachidi S, Metelli A, Riesenberg B, Wu BX, Nelson MH, Wallace C, et al. Platelets subvert T cell immunity against cancer via GARP-TGFbeta axis. Sci Immunol. 2017;2(11). doi: 10.1126/sciimmunol.aai7911 28763790; PubMed Central PMCID: PMC5539882.
20. Salem M, Wallace C, Velegraki M, Li A, Ansa-Addo E, Metelli A, et al. GARP Dampens Cancer Immunity by Sustaining Function and Accumulation of Regulatory T Cells in the Colon. Cancer Res. 2019;79(6):1178–90. doi: 10.1158/0008-5472.CAN-18-2623 30674536; PubMed Central PMCID: PMC6420855.
21. Qin Y, Garrison BS, Ma W, Wang R, Jiang A, Li J, et al. A Milieu Molecule for TGF-beta Required for Microglia Function in the Nervous System. Cell. 2018;174(1):156–71 e16. doi: 10.1016/j.cell.2018.05.027 29909984; PubMed Central PMCID: PMC6089614.
22. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci. 2003;116(Pt 2):217–24. doi: 10.1242/jcs.00229 12482908.
23. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999;96(3):319–28. doi: 10.1016/s0092-8674(00)80545-0 10025398.
24. Mu D, Cambier S, Fjellbirkeland L, Baron JL, Munger JS, Kawakatsu H, et al. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol. 2002;157(3):493–507. Epub 2002/04/22. doi: 10.1083/jcb.200109100 11970960; PubMed Central PMCID: PMC2173277.
25. Noubade R, Wong K, Ota N, Rutz S, Eidenschenk C, Valdez Pa, et al. NRROS negatively regulates reactive oxygen species during host defence and autoimmunity. Nature. 2014;509(7499):235–9. doi: 10.1038/nature13152 24739962
26. Kim JH, Kim K, Kim I, Seong S, Kim N. NRROS Negatively Regulates Osteoclast Differentiation by Inhibiting RANKL-Mediated NF-N:B and Reactive Oxygen Species Pathways. Mol Cells. 2015;38(10):904–10. Epub 2015/10/07. doi: 10.14348/molcells.2015.0177 26442864; PubMed Central PMCID: PMC4625072.
27. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limón P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10(8):554–67. Epub 2010/07/09. doi: 10.1038/nri2808 20616810; PubMed Central PMCID: PMC3885992.
28. Qian L, Wei SJ, Zhang D, Hu X, Xu Z, Wilson B, et al. Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. J Immunol. 2008;181(1):660–8. doi: 10.4049/jimmunol.181.1.660 18566433; PubMed Central PMCID: PMC2741684.
29. Bombara C, Ignotz RA. TGF-beta inhibits proliferation of and promotes differentiation of human promonocytic leukemia cells. J Cell Physiol. 1992;153(1):30–7. doi: 10.1002/jcp.1041530106 1522133.
30. Kamijo R, Takeda K, Nagumo M, Konno K. Effects of combinations of transforming growth factor-beta 1 and tumor necrosis factor on induction of differentiation of human myelogenous leukemic cell lines. J Immunol. 1990;144(4):1311–6. 2105994.
31. Laiho M, Keski-Oja J. Transforming growth factors-beta as regulators of cellular growth and phenotype. Crit Rev Oncog. 1992;3(1–2):1–26. 1312867.
32. Sher A, Gazzinelli RT, Oswald IP, Clerici M, Kullberg M, Pearce EJ, et al. Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev. 1992;127:183–204. doi: 10.1111/j.1600-065x.1992.tb01414.x 1354651.
33. Sheng J, Chen W, Zhu HJ. The immune suppressive function of transforming growth factor-beta (TGF-beta) in human diseases. Growth Factors. 2015;33(2):92–101. doi: 10.3109/08977194.2015.1010645 25714613.
Článek vyšel v časopise
PLOS One
2019 Číslo 10
- Proč se v Česku šíří několik „vymýcených“ infekcí najednou? Ptáme se odborníků
- ADHD jako evoluční výhoda? Výzkum se zaměřil na lovce a sběrače
- Není migréna jako migréna: Co pociťují ženy a co muži?
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Není statin jako statin aneb praktický přehled rozdílů jednotlivých molekul
Nejčtenější v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs)
- Risk factors associated with IgA vasculitis with nephritis (Henoch–Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy