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Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary Research

Basigin-2 upregulated by receptor activator of NF-κB ligand enhances lung cancer-induced osteolytic lesions

Authors: Cheng-Gong Liao, Li Yao, Wei Xie, Lili Liu, Sheng-Da Wu, Ning Lu, Jian-Guo Huang, Ling-Min Kong, He-Long Zhang

Published in: Cancer Cell International | Issue 1/2016

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Abstract

Background

Lung cancer bone metastasis causes poor prognosis. Basigin-2, a novel cancer-associated biomarker, is upregulated in lung cancer and has been linked with tumor progression. But little is known about the role of basigin-2 in lung cancer bone metastasis and osteolytic lesion.

Methods

Basigin-2 expression was evaluated in biopsy tissue specimens of 20 lung cancer patients with bone metastases via immunohistochemistry. Invasion assay and MTT proliferation assay were performed to test the invasion and proliferation of lung cancer cell after modulated basigin-2 expression. The osteoclastic activity of basigin-2 was detected in tibia cancer model by injected of lung cancer cells. The regulation role of receptor activator of NF-κB ligand (RANKL) on basigin-2 and its downstream molecules were measured by real-time quantitative RT-PCR, gelatin zymography and western blot analysis.

Results

We found that basigin-2 was highly expressed in lung cancer bone metastases. Then, we demonstrated that basigin-2 could promote lung cancer cells invasion, metastasis and proliferation through upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression. The lung cancer cells overexpressing basigin-2 strongly induced the osteolytic lesions in immunodeficient mice, which were reduced by treatment with basigin-2 blocking antibody. Furthermore, we explored the enhanced basigin-2 molecular mechanism in lung cancer bone metastasis. Our results indicated the RANKL, pivotal for the control of bone resorption, could increase basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro.

Conclusions

Basigin-2 upregulated by RANKL induces MMPs and VEGF, which may increase lung cancer cell metastasis ability and support osteoclastic activity. Thus, our data suggest important roles for basigin-2 in lung cancer-induced osteolytic lesion and implicate this protein potential application as a target for lung cancer bone metastasis therapy.
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Literature
1.
Araujo A, Ribeiro R, Azevedo I, Coelho A, Soares M, Sousa B, Pinto D, Lopes C, Medeiros R, Scagliotti GV. Genetic polymorphisms of the epidermal growth factor and related receptor in non-small cell lung cancer—a review of the literature. Oncologist. 2007;12(2):201–10.CrossRefPubMed
2.
3.
Groome PA, Bolejack V, Crowley JJ, Kennedy C, Krasnik M, Sobin LH, Goldstraw P, Committee IIS, Cancer R. Biostatistics, observers to the C, participating I: the IASLC lung cancer staging project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thoracic Oncol Off Publ Int Assoc Study Lung Cancer. 2007;2(8):694–705.
4.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
5.
Peters S, Meylan E. Targeting receptor activator of nuclear factor-kappa B as a new therapy for bone metastasis in non-small cell lung cancer. Curr Opin Oncol. 2013;25(2):137–44.CrossRefPubMed
6.
Shi L, Wang L, Hou J, Zhu B, Min Z, Zhang M, Song D, Cheng Y, Wang X. Targeting roles of inflammatory microenvironment in lung cancer and metastasis. Cancer Metastasis Rev. 2015;34(2):319–31.CrossRefPubMed
7.
Clezardin P, Teti A. Bone metastasis: pathogenesis and therapeutic implications. Clin Exp Metastasis. 2007;24(8):599–608.CrossRefPubMed
8.
Sone S, Yano S. Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone. Cancer Metastasis Rev. 2007;26(3–4):685–9.CrossRefPubMed
9.
Kingsley LA, Fournier PG, Chirgwin JM, Guise TA. Molecular biology of bone metastasis. Mol Cancer Ther. 2007;6(10):2609–17.CrossRefPubMed
10.
Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, Nabeshima K. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55(2):434–9.PubMed
11.
Xu HY, Qian AR, Shang P, Xu J, Kong LM, Bian HJ, Chen ZN. siRNA targeted against HAb18G/CD147 inhibits MMP-2 secretion, actin and FAK expression in hepatocellular carcinoma cell line via ERK1/2 pathway. Cancer Lett. 2007;247(2):336–44.CrossRefPubMed
12.
Kasinrerk W, Fiebiger E, Stefanova I, Baumruker T, Knapp W, Stockinger H. Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule. J Immunol. 1992;149(3):847–54.PubMed
13.
Kong LM, Liao CG, Zhang Y, Xu J, Li Y, Huang W, Zhang Y, Bian H, Chen ZN. A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in breast cancer invasion and metastasis. Cancer Res. 2014;74(14):3764–78.CrossRefPubMed
14.
Rucci N, Millimaggi D, Mari M, Del Fattore A, Bologna M, Teti A, Angelucci A, Dolo V. Receptor activator of NF-kappaB ligand enhances breast cancer-induced osteolytic lesions through upregulation of extracellular matrix metalloproteinase inducer/CD147. Cancer Res. 2010;70(15):6150–60.CrossRefPubMed
15.
Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 2001;61(5):2276–81.PubMed
16.
Zhu D, Wang Z, Zhao JJ, Calimeri T, Meng J, Hideshima T, Fulciniti M, Kang Y, Ficarro SB, Tai YT, Hunter Z, McMilin D, Tong H, Mitsiades CS, Wu CJ, Treon SP, Dorfman DM, Pinkus G, Munshi NC, Tassone P, Marto JA, Anderson KC, Carrasco RD. The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat Med. 2015;21(6):572–80.CrossRefPubMedPubMedCentral
17.
Kong LM, Liao CG, Fei F, Guo X, Xing JL, Chen ZN. Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer. Cancer Sci. 2010;101(6):1463–70.CrossRefPubMed
18.
Chen ZN. Significance and application of anti-malignant hepatoma MAb HAb18 in radioimmunal diagnosis of human hepatocellular carcinoma. Zhonghua zhong liu za zhi [Chinese J Oncol]. 1992;14(1):9–12.
19.
Ku XM, Liao CG, Li Y, Yang XM, Yang B, Yao XY, Wang L, Kong LM, Zhao P, Chen ZN. Epitope mapping of series of monoclonal antibodies against the hepatocellular carcinoma-associated antigen HAb18G/CD147. Scand J Immunol. 2007;65(5):435–43.CrossRefPubMed
20.
Liao CG, Kong LM, Song F, Xing JL, Wang LX, Sun ZJ, Tang H, Yao H, Zhang Y, Wang L, Wang Y, Yang XM, Li Y, Chen ZN. Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion. Mol Cell Biol. 2011;31(13):2591–604.CrossRefPubMedPubMedCentral
21.
Bian H, Zheng JS, Nan G, Li R, Chen C, Hu CX, Zhang Y, Sun B, Wang XL, Cui SC, Wu J, Xu J, Wei D, Zhang X, Liu H, Yang W, Ding Y, Li J, Chen ZN. Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation. J Natl Cancer Inst. 2014;106(9):dju239.CrossRefPubMed
22.
Fei F, Li X, Xu L, Li D, Zhang Z, Guo X, Yang H, Chen Z, Xing J. CD147–CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway. Ann Surg Oncol. 2014;21(13):4359–68.CrossRefPubMed
23.
24.
Marzia M, Sims NA, Voit S, Migliaccio S, Taranta A, Bernardini S, Faraggiana T, Yoneda T, Mundy GR, Boyce BF, Baron R, Teti A. Decreased c-Src expression enhances osteoblast differentiation and bone formation. J Cell Biol. 2000;151(2):311–20.CrossRefPubMedPubMedCentral
25.
Zhao P, Zhang W, Wang SJ, Yu XL, Tang J, Huang W, Li Y, Cui HY, Guo YS, Tavernier J, Zhang SH, Jiang JL, Chen ZN. HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells. Hepatology. 2011;54(6):2012–24.CrossRefPubMed
26.
Kong LM, Liao CG, Chen L, Yang HS, Zhang SH, Zhang Z, Bian HJ, Xing JL, Chen ZN. Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma. J Cell Mol Med. 2011;15(6):1415–28.CrossRefPubMedPubMedCentral
27.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
28.
Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, Wu M, Pan Z, Zhou W. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103(8):1215–20.CrossRefPubMedPubMedCentral
29.
Angelucci A, Gravina GL, Rucci N, Festuccia C, Muzi P, Vicentini C, Teti A, Bologna M. Evaluation of metastatic potential in prostate carcinoma: an in vivo model. Int J Oncol. 2004;25(6):1713–20.PubMed
30.
Damsker JM, Okwumabua I, Pushkarsky T, Arora K, Bukrinsky MI, Constant SL. Targeting the chemotactic function of CD147 reduces collagen-induced arthritis. Immunology. 2009;126(1):55–62.CrossRefPubMedPubMedCentral
31.
Chen LM, Kuo CH, Lai TY, Lin YM, Su CC, Hsu HH, Tsai FJ, Tsai CH, Huang CY, Tang CH. RANKL increases migration of human lung cancer cells through intercellular adhesion molecule-1 up-regulation. J Cell Biochem. 2011;112(3):933–41.CrossRefPubMed
32.
da Silva GT, Bergmann A, Thuler LC. Skeletal related events in patients with bone metastasis arising from non-small cell lung cancer. Supportive Care Cancer Off J Multinatl Assoc Support Care Cancer. 2015.
33.
Sathiakumar N, Delzell E, Morrisey MA, Falkson C, Yong M, Chia V, Blackburn J, Arora T, Kilgore ML. Mortality following bone metastasis and skeletal-related events among patients 65 years and above with lung cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999–2006. Lung India Off Organ Indian Chest Soc. 2013;30(1):20–6.CrossRef
34.
Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG, Kim CH. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 2004;18(14):1670–81.CrossRefPubMed
35.
Bhattacharya R, Sinha S, Yang SP, Patra C, Dutta S, Wang E, Mukhopadhyay D. The neurotransmitter dopamine modulates vascular permeability in the endothelium. J Mol Signaling. 2008;3:14.CrossRef
36.
Zhai R, Liu G, Zhou W, Su L, Heist RS, Lynch TJ, Wain JC, Asomaning K, Lin X, Christiani DC. Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(2):612–7.CrossRef
37.
Roodman GD. Mechanisms of bone metastasis. New England J Med. 2004;350(16):1655–64.CrossRef
38.
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.CrossRefPubMed
39.
Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4(8):638–49.CrossRefPubMed
Metadata
Title
Basigin-2 upregulated by receptor activator of NF-κB ligand enhances lung cancer-induced osteolytic lesions
Authors
Cheng-Gong Liao
Li Yao
Wei Xie
Lili Liu
Sheng-Da Wu
Ning Lu
Jian-Guo Huang
Ling-Min Kong
He-Long Zhang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0302-9

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