Two Gln187 mutants of human soluble APRIL inhibit proliferation of lung carcinoma A549 cells

• Autorzy: Dai S. , Zheng Y. , Chen B. , Gao M. , Zhang Y. , Zhang L. , Gong W. , He F.
• Języki publikacji: EN

Abstrakty

EN

 Soluble APRIL (sAPRIL), the active form of a proliferation-inducing ligand (APRIL), is implicated in the proliferation of tumor cells. Suppressing APRIL function has been considered as a potential strategy for the therapy of APRIL-associated tumors. In the present study, we generated human sAPRIL and its two mutants, Gln187-D-sAPRIL (Gln187 deleted) and Gly187-sAPRIL (Gln187 replaced by Gly). In vitro experiments showed that the two mutants had similar specific binding capacity to lung carcinoma A549 cells compared to the wild-type sAPRIL, and both, especially Gly187-sAPRIL, exhibited significant antagonistic effect on sAPRIL-induced tumor cell proliferation in a dose-dependent manner, which might be predominantly mediated by blocking sAPRIL-induced MEK and ERK phosphorylation but not p38MAPK or JNK signaling. In vivo experiments with nude mice bearing A549 cell-derived xenograft tumor showed that only the Gly187-sAPRIL mutant could significantly suppress the tumor growth. These results suggest that Gln187 may be a crucial amino acid in APRIL-mediated tumor cell proliferation via the MEK-ERK signaling pathway and that the sAPRIL mutants may serve as novel potential antagonists of APRIL for the therapy of APRIL-associated cancers.

Słowa kluczowe

EN

lung carcinoma; S549 cell; tumour growth; tumour necrosis factor; Gln187 mutant; proliferation-inducing ligand; antitumour activity; tumour cell

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2009
• Tom: 56
• Numer: 4
• Opis fizyczny: p.703-710,fig.,ref.

Twórcy

autor

Dai S.

• Third Military Medical University, 30 Gaotanyan, Shapingba, Chongqing 400038, China

autor

Zheng Y.

autor

Chen B.

autor

Gao M.

autor

Zhang Y.

autor

Zhang L.

autor

Gong W.

autor

He F.

Bibliografia

• Bonci D, Hahne M, Felli N, Peschle C, De-Maria R (2004) Potential role of APRIL as autocrine growth factor for megakaryocytopoiesis. Blood 104: 3169-3172. 
• Chen Y, Leask A, Abraham DJ, Pala D, Shiwen X, Khan K, Liu S, Carter DE, Wilcox-Adelman S, Goetinck P, Denton CP, Black CM, Pitsillides AA, Sarraf CE, Eastwood M (2008) Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts. Arthritis Rheum 58: 577-585. 
• Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26: 3279-3290. 
• Gao H, Fu W, Li R, Chen L, Ji Q, Zhang L, Huang G, He F (2006) Expression and purification of a soluble B lymphocyte stimulator mutant modified with the T-helper cell epitope. Biotechnol Lett 28: 1649-1654. 
• Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J (1998) APRIL, a new ligand of the tumor necrosis factor family, stimulates cell growth. J Exp Med 188: 1185-1190. 
• Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP (2005) Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation. Cell Death Differ 12: 637-648. 
• Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F, Gorelik L, Kalled SL, Acha-Orbea H, Rennert PD, Tschopp J, Schneider P (2005) Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med 201: 1375-1383. 
• Ito Y, Sasaki Y, Horimoto M, Wada S, Tanaka Y, Kasahara A, Ueki T, Hirano T, Yamamoto H, Fujimoto J, Okamoto E, Hayashi N, Hori M (1998) Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology 27: 951-958. 
• Iłzecka J, Iłzecki M (2006) APRIL is increased in serum of patients with brain glioblastoma multiforme. Eur Cytokine Netw 17: 276-280. 
• Kalled SL, Ambrose C, Hsu YM (2005) The biochemistry and biology of BAFF, APRIL and their receptors. Curr Dir Autoimmun 8: 206-242. 
• Liu Y, Xu L, Opalka N, Kappler J, Shu HB, Zhang G (2002) Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands. Cell 108: 383-394. 
• López-Fraga M, Fernández R, Albar JP, Hahne M (2001) Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep 2: 945-951. 
• Mackay F, Ambrose C (2003) The TNF family members BAFF and APRIL: the growing complexity. Cytokine Growth Factor Rev 14: 311-324. 
• Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A (2000) Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI. Curr Biol 10: 785-788. 
• Medema JP, Planelles-Carazo L, Hardenberg G, Hahne M (2003) The uncertain glory of APRIL. Cell Death Differ 10: 1121-1125. 
• Planelles L, Castillo-Gutiérrez S, Medema JP, Morales-Luque A, Merle-Béral H, Hahne M (2007) APRIL but not BLyS serum levels are increased in chronic lymphocytic leukemia: prognostic relevance of APRIL for survival. Haematologica 92: 1284-1285. 
• Rabenstein DL (2002) Heparin and heparan sulfate: structure and function. Nat Prod Rep 19: 312-331. 
• Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, Holler N, Qian F, Mullen C, Strauch K, Browning JL, Ambrose C, Tschopp J (2000) A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med 192: 1677-1683. 
• Roosnek E, Burjanadze M, Dietrich PY, Matthes T, Passweg J, Huard B (2009) Tumors that look for their springtime in APRIL. Crit Rev Oncol Hematol 72: 91-97. 
• Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M (2001) APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis. Cell Death Differ 8: 403-410. 
• Schwaller J, Schneider P, Mhawech-Fauceglia P, McKee T, Myit S, Matthes T, Tschopp J, Donze O, Le Gal FA, Huard B (2007) Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness. Blood 109: 331-338. 
• Stein JV, López-Fraga M, Elustondo FA, Carvalho-Pinto CE, Rodríguez D, Gómez-Caro R, De Jong J, Martínez-A C, Medema JP, Hahne M (2002) APRIL modulates B and T cell immunity. J Clin Invest 109: 1587-1598. 
• Trabach L, Lugovskoy A, Vlijmen HV, Dejardin E, Kalled SL, Rennert P (2002) APRIL and BAFF are members of a unique subfamily within the TNF family of proteins. Curr Trends Immunol 4: 25-45.
• Wallweber HJ, Compaan DM, Starovasnik MA, Hymowitz SG (2004) The crystal structure of a proliferation-inducing ligand, APRIL. J Mol Biol 343: 283-290. 
• Wingfield PT (1995) Overview of the purification of recombinant proteins produced in Escherichia coli. In Current protocols in protein science. Coligan JE, Dunn BM, Ploegh HL, Speicher DW, Wingfield PT, eds, vol 1, pp 6.1.1-6.1.22, John Wiley and Sons, New York.
• Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE (2000) APRIL and TALL-I and receptors BCMA and TACI: System for regulating humoral immunity. Nat Immunol 1: 252-256