Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration and invasion

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• 作者：Shilpa S. Patil ; Reema Railkar ; Monalisa Swain…
• 关键词：IGFBP2 ; scFv ; Glioma ; Invasion
• 刊名：Journal of Neuro-Oncology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：123
• 期：2
• 页码：225-235
• 全文大小：2,040 KB
• 参考文献：1.Arimappamagan A, Somasundaram K, Thennarasu K, Peddagangannagari S, Srinivasan H, Shailaja BC, Samuel C, Patric IRP, Shukla S, Thota B, Prasanna KV, Pandey P, Balasubramaniam A, Santosh V, Chandramouli BA, Hegde AS, Kondaiah P, Sathyanarayana Rao MR (2013) A fourteen gene GBM prognostic signature identifies association of immune response pathway and mesenchymal subtype with high risk group. PLoS One 8(4):e62042View Article PubMed Central PubMed
  2.Kim Y, Koul D, Kim SH, Lucio-eterovic AK, Freire PR, Yao J, Wang J, Almeida JS, Aldape K, Yung WKA (2013) Identification of prognostic gene signatures data analysis. Neuro Oncol 15(7):829-39View Article PubMed Central PubMed
  3.Sehgal P, Kumar N, Praveen Kumar VR, Patil S, Bhattacharya A, Vijaya Kumar M, Mukherjee G, Kondaiah P (2013) Regulation of protumorigenic pathways by insulin like growth factor binding protein2 and its association along with β-catenin in breast cancer lymph node metastasis. Mol Cancer 12(1):63View Article PubMed Central PubMed
  4.Santosh V, Arivazhagan A, Sreekanthreddy P, Srinivasan H, Thota B, Srividya MR, Vrinda M, Sridevi S, Shailaja BC, Samuel C, Prasanna KV, Thennarasu K, Balasubramaniam A, Chandramouli BA, Hegde AS, Somasundaram K, Kondaiah P, Rao MRS (2010) Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma. Cancer Epidemiol Biomarkers Prev 19(6):1399-408View Article PubMed
  5.Russo VC, Schütt BS, Andaloro E, Ymer SI, Hoeflich A, Ranke MB, Bach LA, Werther GA (2005) Insulin-like growth factor binding protein-2 binding to extracellular matrix plays a critical role in neuroblastoma cell proliferation, migration, and invasion. Endocrinology 146(10):4445-455View Article PubMed
  6.Fukushima T, Tezuka T, Shimomura T, Nakano S, Kataoka H (2007) Silencing of insulin-like growth factor-binding protein-2 in human glioblastoma cells reduces both invasiveness and expression of progression-associated gene CD24. J Biol Chem 282(25):18634-8644View Article PubMed
  7.Lee E-J, Mircean C, Shmulevich I, Wang H, Liu J, Niemist? A, Kavanagh JJ, Lee J-H, Zhang W (2005) Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion. Mol Cancer 4(1):7View Article PubMed Central PubMed
  8.Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou Y, Liao WS, Fuller GN, Zhang W (2003) Advances in brief insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes 1. Cancer Res 63:4315-321PubMed
  9.Song SW, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lang FF, Zhang W (2003) IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion. Proc Natl Acad Sci U S A 100(24):13970-3975View Article PubMed Central PubMed
  10.Lin Y, Jiang T, Zhou K, Xu L, Chen B, Li G, Qiu X, Jiang T, Zhang W, Song SW (2009) Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas. Neuro Oncol 11(5):468-76View Article PubMed Central PubMed
  11.Elmlinger MW, Deininger MH, Schuett BS, Meyermann R, Duffner F, Grote EH, Ranke MB (2001) In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 142(4):1652-658PubMed
  12.Perks CM, Vernon EG, Rosendahl AH, Tonge D, Holly JMP (2007) IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells. Oncogene 26(40):5966-972View Article PubMed
  13.Migita T, Narita T, Asaka R, Miyagi E, Nagano H, Nomura K, Matsuura M, Satoh Y, Okumura S, Nakagawa K, Seimiya H, Ishikawa Y (2010) Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma: IGF-independent antiapoptotic effect via caspase-3. Am J Pathol 176(4):1756-766View Article PubMed Central PubMed
  14.Uzoh CC, Holly JMP, Biernacka KM, Persad RA, Bahl A, Gillatt D, Perks CM (2011) Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel. Br J Cancer 104(10):1587-593View Article PubMed Central PubMed
  15.Mendes KN, Wang GK, Fuller GN, Zhang W (2010) JNK mediates insulin-like growth factor binding protein 2/integrin alpha5-dependent glioma cell migration. Int J Oncol 37(1):143-53PubMed
  16.Wang GK, Hu L, Fuller GN, Zhang W (2006) An interaction between insulin-like growth factor-binding protein 2 (IGFBP2) and integrin alpha5 is essential for IGFBP2-induced cell mobility. J Biol Chem 281(20):14085-4091View Article PubMed
  17.Forbes BE, McCarthy P, Norton RS (2012) Insulin-like growth factor binding proteins: a structural perspective. Front Endocrinol (Lausanne) 3:38
  18.Han S, Li Z, Master LM, Master ZW, Wu A (2014) Exogenous IGFBP-2 promotes proliferation, invasion, and chemoresistance to temozolomide in gli
• 作者单位：Shilpa S. Patil (1)
  Reema Railkar (1)
  Monalisa Swain (2)
  Hanudatta S. Atreya (2)
  Rajan R. Dighe (1)
  Paturu Kondaiah (1)
  
  1. Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore, 560012, India
  2. NMR Research Centre, Indian Institute of Science, Bangalore, 560012, India
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7373

文摘

Insulin like growth factor binding protein 2 (IGFBP2) is highly up regulated in glioblastoma (GBM) tissues and has been one of the prognostic indicators. There are compelling evidences suggesting important roles for IGFBP2 in glioma cell proliferation, migration and invasion. Extracellular IGFBP2 through its carboxy terminal arginine glycine aspartate (RGD) motif can bind to cell surface α5β1 integrins and activate pathways downstream to integrin signaling. This IGFBP2 activated integrin signaling is known to play a crucial role in IGFBP2 mediated invasion of glioma cells. Hence a molecular inhibitor of carboxy terminal domain of IGFBP2 which can inhibit IGFBP2-cell surface interaction is of great therapeutic importance. In an attempt to develop molecular inhibitors of IGFBP2, we screened single chain variable fragment (scFv) phage display libraries, Tomlinson I (Library size 1.47?×?108) and Tomlinson J (Library size 1.37?×?108) using human recombinant IGFBP2. After screening we obtained three IGFBP2 specific binders out of which one scFv B7J showed better binding to IGFBP2 at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced activity of matrix metalloprotease 2 in the conditioned medium of glioma cells and inhibited IGFBP2 induced migration and invasion of glioma cells. We demonstrate for the first time that in vitro inhibition of extracellular IGFBP2 activity by using human scFv results in significant reduction of glioma cell migration and invasion. Therefore, the inhibition of IGFBP2 can serve as a potential therapeutic strategy in the management of GBM.