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Progranulin as a Potential Biomarker of Central Nervous System Disease

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Progranulin and Central Nervous System Disorders

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Abstract

Progranulin is a cysteine-rich secreted protein initially identified as a growth factor. Progranulin has been implicated in multiple biological and pathological processes, including tumorigenesis, inflammation, neurodegeneration and lysosomal function. Loss of one allele of the progranulin gene (GRN) leads to frontotemporal lobar degeneration (FTLD). GRN null mutations cause haploinsufficiency, leading to a significant decrease in progranulin protein levels in the plasma, serum and cerebrospinal fluid (CSF) of carriers. Recently, several reports have shown that plasma progranulin levels predict GRN mutation status in patients with FTLD and asymptomatic family members. Thus, the concentration of circulating progranulin is a useful biomarker for screening GRN mutation carriers. Interestingly, there are also conditions in which expression of progranulin is increased. For example, progranulin is highly overexpressed in aggressive cancer cell lines and tissue specimens from various malignancies. Furthermore, progranulin expression in tumor and serum samples correlates with pathological grading and prognosis in several types of cancer. In the central nervous system (CNS), progranulin is often highly expressed in gliomas. Recently, we reported increased progranulin levels in the CSF of patients with CNS lymphomas and carcinomas with CNS metastasis. Accordingly, CSF progranulin levels may be useful as a diagnostic and monitoring marker for CNS metastases of lymphomas and carcinomas. Progranulin is also associated with various autoimmune diseases. For example, in rheumatoid arthritis and systemic lupus erythematosus, progranulin serum levels positively correlate with disease activity. Several reports also suggest an association with autoimmune CNS diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Increased CSF progranulin levels are observed in the acute phase of these diseases. Additionally, although still controversial, increased progranulin levels appear to be associated with remission of symptoms in MS and NMOSD. Therefore, progranulin may be a promising therapeutic agent and useful biomarker of CNS diseases, including GRN-related neurodegenerative diseases, malignancies, and autoimmune neurological disorders.

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References

  • Abella V, Pino J, Scotece M, Conde J, Lago F, Gonzalez-Gay MA, Mera A, Gómez R, Mobasheri A, Gualillo O (2017) Progranulin as a biomarker and potential therapeutic agent. Drug Discov Today 22(10):1557–1564. https://doi.org/10.1016/j.drudis

    Article  CAS  PubMed  Google Scholar 

  • Ahluwalia MS, Wallace PK, Peereboom DM (2012) Flow cytometry as a diagnostic tool in lymphomatous or leukemic meningitis: ready for prime time? Cancer 118:1747–1753. https://doi.org/10.1002/cncr.26335

    Article  PubMed  Google Scholar 

  • Almeida MR, Macário MC, Ramos L, Baldeiras I, Ribeiro MH, Santana I (2016) Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation. Neurobiol Aging 41:200.e1–200.e5. https://doi.org/10.1016/j.neurobiolaging.2016.02.019

    Article  CAS  PubMed  Google Scholar 

  • Arechavaleta-Velasco F, Perez-Juarez CE, Gerton GL, Diaz-Cueto L (2017) Progranulin and its biological effects in cancer. Med Oncol 34(12):194. https://doi.org/10.1007/s12032-017-1054-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aviles A, Gómez R, Salas J (1991) Ferritin in the cerebrospinal fluid as an early indicator of neuromeningeal involvement in patients with malignant lymphoma. Gac Med Mex 127:249–252 [In Spanish]

    Google Scholar 

  • Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442(7105):916–919

    Article  CAS  Google Scholar 

  • Bandey I, Chiou SH, Huang AP, Tsai JC, Tu PH (2015) Progranulin promotes Temozolomide resistance of glioblastoma by orchestrating DNA repair and tumor stemness. Oncogene 34(14):1853–1864. https://doi.org/10.1038/onc.2014.92

    Article  CAS  PubMed  Google Scholar 

  • Baraniskin A, Kuhnhenn J, Schlegel U, Chan A, Deckert M, Gold R, Maghnouj A, Zöllner H, Reinacher-Schick A, Schmiegel W, Hahn SA, Schroers R (2011) Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 117:3140–3146. https://doi.org/10.1182/blood-2010-09-308684

    Article  CAS  PubMed  Google Scholar 

  • Berghoff AS, Stefanits H, Woehrer A, Heinzl H, Preusser M, Hainfellner JA, Vienna Comprehensive Cancer Center Central Nervous System Unit (2013) Clinical neuropathology practice guide 3-2013: levels of evidence and clinical utility of prognostic and predictive candidate brain tumor biomarkers. Clin Neuropathol 32:148–158

    Article  Google Scholar 

  • Carecchio M, Fenoglio C, Cortini F, Comi C, Benussi L, Ghidoni R, Borroni B, De Riz M, Serpente M, Cantoni C, Franceschi M, Albertini V, Monaco F, Rainero I, Binetti G, Padovani A, Bresolin N, Scarpini E, Galimberti D (2011) Cerebrospinal fluid biomarkers in Progranulin mutations carriers. J Alzheimers Dis 27(4):781–790. https://doi.org/10.3233/JAD-2011-111046

    Article  CAS  PubMed  Google Scholar 

  • Carlson AM, Maurer MJ, Goergen KM, Kalli KR, Erskine CL, Behrens MD, Knutson KL, Block MS (2013) Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer. Cancer Epidemiol Biomark Prev 22(10):1730–1735. https://doi.org/10.1158/1055-9965.EPI-12-1368

    Article  CAS  Google Scholar 

  • Cenik B, Sephton CF, Kutluk Cenik B, Herz J, Yu G (2012) Progranulin: a proteolytically processed protein at the crossroads of inflammation and neurodegeneration. J Biol Chem 287(39):32298–32306

    Article  CAS  Google Scholar 

  • Chen XY, Li JS, Liang QP, He DZ, Zhao J (2008) Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J 121(10):881–886

    Article  CAS  Google Scholar 

  • Chitramuthu BP, Bennett HPJ, Bateman A (2017) Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease. Brain 140(12):3081–3104. https://doi.org/10.1093/brain/awx198

    Article  PubMed  Google Scholar 

  • Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442(7105):920–924

    Article  CAS  Google Scholar 

  • Cuevas-Antonio R, Cancino C, Arechavaleta-Velasco F, Andrade A, Barron L, Estrada I, Fernandez RL, Olguin V, Ruiz S, Imani F, Zeferino-Toquero M, Ulloa-Aguirre A, Gerton GL, Diaz-Cueto L (2010) Expression of progranulin (acrogranin/PCDGF/granulin-epithelin precursor) in benign and malignant ovarian tumors and activation of MAPK signaling in ovarian cancer cell line. Cancer Investig 28(5):452–458. https://doi.org/10.3109/07357900903346455

    Article  CAS  Google Scholar 

  • De Riz M, Galimberti D, Fenoglio C, Piccio LM, Scalabrini D, Venturelli E, Pietroboni A, Piola M, Naismith RT, Parks BJ, Fumagalli G, Bresolin N, Cross AH, Scarpini E (2010) Cerebrospinal fluid progranulin levels in patients with different multiple sclerosis subtypes. Neurosci Lett 469(2):234–236. https://doi.org/10.1016/j.neulet.2009.12.002

    Article  CAS  PubMed  Google Scholar 

  • Donald CD, Laddu A, Chandham P, Lim SD, Cohen C, Amin M, Gerton GL, Marshall FF, Petros JA (2001) Expression of progranulin and the epithelin/granulin precursor acrogranin correlates with neoplastic state in renal epithelium. Anticancer Res 21(6A):3739–3742

    CAS  PubMed  Google Scholar 

  • Edelman MJ, Feliciano J, Yue B, Bejarano P, Ioffe O, Reisman D, Hawkins D, Gai Q, Hicks D, Serrero G (2014) GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol 45:1893–1899. https://doi.org/10.1016/j.humpath.2014.05.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eriksen JL, Mackenzie IR (2008) Progranulin: normal function and role in neurodegeneration. J Neurochem 104(2):287–297

    CAS  PubMed  Google Scholar 

  • Fenoglio C, Scalabrini D, Esposito F, Comi C, Cavalla P, De Riz M, Martinelli V, Piccio LM, Venturelli E, Fumagalli G, Capra R, Collimedaglia L, Ghezzi A, Rodegher ME, Vercellino M, Leone M, Giordana MT, Bresolin N, Monaco F, Comi G, Scarpini E, Martinelli-Boneschi F, Galimberti D (2010) Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males. Genes Immun 11(6):497–503. https://doi.org/10.1038/gene.2010.18

    Article  CAS  PubMed  Google Scholar 

  • Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, Bisceglio G, Rovelet-Lecrux A, Boeve B, Petersen RC, Dickson DW, Younkin SG, Deramecourt V, Crook J, Graff-Radford NR, Rademakers R (2009) Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 132(Pt 3):583–591. https://doi.org/10.1093/brain/awn352

    Article  PubMed  PubMed Central  Google Scholar 

  • Fischer L, Korfel A, Pfeiffer S, Kiewe P, Volk HD, Cakiroglu H, Widmann T, Thiel E (2009) CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin Cancer Res 15:5968–5973. https://doi.org/10.1158/1078-0432.CCR-09-0108

    Article  CAS  PubMed  Google Scholar 

  • Frampton G, Invernizzi P, Bernuzzi F, Pae HY, Quinn M, Horvat D, Galindo C, Huang L, McMillin M, Cooper B, Rimassa L, DeMorrow S (2012) Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism. Gut 61(2):268–277. https://doi.org/10.1136/gutjnl-2011-300643

    Article  CAS  PubMed  Google Scholar 

  • Galimberti D, Fumagalli GG, Fenoglio C, Cioffi SMG, Arighi A, Serpente M, Borroni B, Padovani A, Tagliavini F, Masellis M, Tartaglia MC, van Swieten J, Meeter L, Graff C, de Mendonça A, Bocchetta M, Rohrer JD, Scarpini E, Genetic FTD Initiative (GENFI) (2018) Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study. Neurobiol Aging 62:245.e9–245.e12. https://doi.org/10.1016/j.neurobiolaging.2017.10.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M, Adamson J, Crook R, Melquist S, Kuntz K, Petersen R, Josephs K, Pickering-Brown SM, Graff-Radford N, Uitti R, Dickson D, Wszolek Z, Gonzalez J, Beach TG, Bigio E, Johnson N, Weintraub S, Mesulam M, White CL 3rd, Woodruff B, Caselli R, Hsiung GY, Feldman H, Knopman D, Hutton M, Rademakers R (2006) Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Mol Genet 15(20):2988–3001

    Article  CAS  Google Scholar 

  • Ghidoni R, Benussi L, Glionna M, Franzoni M, Binetti G (2008) Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 71(16):1235–1239. https://doi.org/10.1212/01.wnl.0000325058.10218.fc

    Article  CAS  PubMed  Google Scholar 

  • Ghidoni R, Stoppani E, Rossi G, Piccoli E, Albertini V, Paterlini A, Glionna M, Pegoiani E, Agnati LF, Fenoglio C, Scarpini E, Galimberti D, Morbin M, Tagliavini F, Binetti G, Benussi L (2012a) Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: a multicenter Italian study. Neurodegener Dis 9(3):121–127. https://doi.org/10.1159/000333132

    Article  CAS  PubMed  Google Scholar 

  • Ghidoni R, Paterlini A, Benussi L (2012b) Circulating progranulin as a biomarker for neurodegenerative diseases. Am J Neurodegener Dis 1(2):180–190

    PubMed  PubMed Central  Google Scholar 

  • Göbel M, Eisele L, Möllmann M, Hüttmann A, Johansson P, Scholtysik R, Bergmann M, Busch R, Döhner H, Hallek M, Seiler T, Stilgenbauer S, Klein-Hitpass L, Dührsen U, Dürig J (2013) Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. PLoS One 8:e72107. https://doi.org/10.1371/journal.pone.0072107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han JJ, Yu M, Houston N, Steinberg SM, Kohn EC (2011) Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol 120:5–10. https://doi.org/10.1016/j.ygyno.2010.09.006

    Article  CAS  PubMed  Google Scholar 

  • Hansen PB, Kjeldsen L, Dalhoff K, Olesen B (1992) Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma: a useful marker in early diagnosis and monitoring of CNS-involvement. Acta Neurol Scand 85:224–227

    Article  CAS  Google Scholar 

  • He Z, Bateman A (1999) Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res 59(13):3222–3229

    CAS  PubMed  Google Scholar 

  • Ho JC, Ip YC, Cheung ST, Lee YT, Chan KF, Wong SY, Fan ST (2008) Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology 47(5):1524–1532. https://doi.org/10.1002/hep.22191

    Article  CAS  PubMed  Google Scholar 

  • Içöz S, Tüzün E, Kürtüncü M, DurmuÅŸ H, Mutlu M, Eraksoy M, Akman-Demir G (2010) Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients. Int J Neurosci 120(1):71–75. https://doi.org/10.3109/00207450903428970

    Article  PubMed  Google Scholar 

  • Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, Rommer P, Kleiter I, Stich O, Reuss R, Rauer S, Zettl UK, Wandinger KP, Melms A, Aktas O, Kristoferitsch W, Wildemann B (2011) Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci 306(1–2):82–90. https://doi.org/10.1016/j.jns.2011.03.038

    Article  CAS  PubMed  Google Scholar 

  • Jian J, Konopka J, Liu C (2013a) Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol 93(2):199–208. https://doi.org/10.1189/jlb.0812429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jian J, Zhao S, Tian Q, Gonzalez-Gugel E, Mundra JJ, Uddin SM, Liu B, Richbourgh B, Brunetti R, Liu CJ (2013b) Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains. FEBS Lett 587(21):3428–3436. https://doi.org/10.1016/j.febslet.2013.09.024

    Article  CAS  PubMed  Google Scholar 

  • Jian J, Li G, Hettinghouse A, Liu C (2018) Progranulin: a key player in autoimmune diseases. Cytokine 101:48–55. https://doi.org/10.1016/j.cyto.2016.08.007

    Article  CAS  PubMed  Google Scholar 

  • Katz SI (2016) Neuromyelitis optica spectrum disorders. Continuum (Minneap Minn) 22(3):864–896. https://doi.org/10.1212/CON.0000000000000337

    Article  Google Scholar 

  • Kim CH, Cheong JH, Kim JM (2010) Correlation of granulin expression in intracranial meningiomas to clinical parameters. Exp Ther Med 1(3):493–496

    Article  CAS  Google Scholar 

  • Kim JH, Do IG, Kim K, Sohn JH, Kim HJ, Jeon WK, Lee SR, Son BH, Shin JH, Nam H, Kwon HJ, Kim MS, Hong HP, Serrero G, Koo DH, KBSMC Pancreatobiliary Cancer Team (2012) Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma. Cancer Chemother Pharmacol 78(5):1085–1092

    Article  CAS  Google Scholar 

  • Kimura A, Takemura M, Saito K, Serrero G, Yoshikura N, Hayashi Y, Inuzuka T (2017) Increased cerebrospinal fluid progranulin correlates with interleukin-6 in the acute phase of neuromyelitis optica spectrum disorder. J Neuroimmunol 305:175–181. https://doi.org/10.1016/j.jneuroim.2017.01.006

    Article  CAS  PubMed  Google Scholar 

  • Kimura A, Takemura M, Serrero G, Yoshikura N, Hayashi Y, Saito K, Inuzuka T (2018) Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and carcinoma with CNS metastasis. J Neurooncol doi 137:455–462. https://doi.org/10.1007/s11060-017-2742-z

    Article  CAS  Google Scholar 

  • Koo DH, Park CY, Lee ES, Ro J, Oh SW (2012) Progranulin as a prognostic biomarker for breast cancer recurrence in patients who had hormone receptor-positive tumors: a cohort study. PLoS One 7:e39880. https://doi.org/10.1371/journal.pone.0039880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee W, Kim SJ, Lee S, Kim J, Kim M, Lim J, Kim Y, Cho B, Lee EJ, Han K (2005) Significance of cerebrospinal fluid sIL-2R level as a marker of CNS involvement in acute lymphoblastic leukemia. Ann Clin Lab Sci 35:407–412

    CAS  PubMed  Google Scholar 

  • Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202(4):473–477

    Article  CAS  Google Scholar 

  • Li LQ, Huang HL, Ping JL, Wang XH, Zhong J, Dai LC (2011) Clinicopathologic and prognostic implications of progranulin in breast carcinoma. Chin Med J 124(13):2045–2050

    CAS  PubMed  Google Scholar 

  • Li LQ, Min LS, Jiang Q, Ping JL, Li J, Dai LC (2012) Progranulin expression in breast cancer with different intrinsic subtypes. Pathol Res Pract 208(4):210–216. https://doi.org/10.1016/j.prp.2012.02.001

    Article  CAS  PubMed  Google Scholar 

  • Liu CJ, Bosch X (2012) Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 133(1):124–132. https://doi.org/10.1016/j.pharmthera.2011.10.003

    Article  CAS  PubMed  Google Scholar 

  • Lovat F, Bitto A, Xu SQ, Fassan M, Goldoni S, Metalli D, Wubah V, McCue P, Serrero G, Gomella LG, Baffa R, Iozzo RV, Morrione A (2009) Proepithelin is an autocrine growth factor for bladder cancer. Carcinogenesis 30(5):861–868. https://doi.org/10.1093/carcin/bgp050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Zheng L, Zhang W, Feng T, Liu J, Wang X, Yu Y, Qi M, Zhao W, Yu X, Tang W (2014) Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro. Gynecol Oncol 134(2):364–371. https://doi.org/10.1016/j.ygyno.2014.05.025

    Article  CAS  PubMed  Google Scholar 

  • Matsumura N, Mandai M, Miyanishi M, Fukuhara K, Baba T, Higuchi T, Kariya M, Takakura K, Fujii S (2006) Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in in vivo tumorigenesis. Clin Cancer Res 12(5):1402–1411

    Article  CAS  Google Scholar 

  • McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ, Work Group on Frontotemporal Dementia and Pick’s Disease (2001) Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58(11):1803–1809

    Article  CAS  Google Scholar 

  • Murchison A, Kitley J, Leite MI, Küker W, Palace J (2015) Predictive value of MRI parameters in severity and recovery of first-episode myelitis in aquaporin-4 antibody disease. J Neurol Sci 355(1–2):49–53. https://doi.org/10.1016/j.jns.2015.05.011

    Article  PubMed  Google Scholar 

  • Ong CH, Bateman A (2003) Progranulin (granulin–epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. Histol Histopathol 18:1275–1288. https://doi.org/10.14670/HH-18.1275

    Article  CAS  PubMed  Google Scholar 

  • Pan CX, Kinch MS, Kiener PA, Langermann S, Serrero G, Sun L, Corvera J, Sweeney CJ, Li L, Zhang S, Baldridge LA, Jones TD, Koch MO, Ulbright TM, Eble JN, Cheng L (2004) PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Clin Cancer Res 10(4):1333–1337

    Article  CAS  Google Scholar 

  • Perry DC, Lehmann M, Yokoyama JS, Karydas A, Lee JJ, Coppola G, Grinberg LT, Geschwind D, Seeley WW, Miller BL, Rosen H, Rabinovici G (2013) Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 70(6):774–778. https://doi.org/10.1001/2013.jamaneurol.393

    Article  PubMed  PubMed Central  Google Scholar 

  • Roy S, Josephson SA, Fridlyand J, Karch J, Kadoch C, Karrim J, Damon L, Treseler P, Kunwar S, Shuman MA, Jones T, Becker CH, Schulman H, Rubenstein JL (2008) Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol 26:96–105

    Article  CAS  Google Scholar 

  • Rubenstein JL, Wong VS, Kadoch C, Gao HX, Barajas R, Chen L, Josephson SA, Scott B, Douglas V, Maiti M, Kaplan LD, Treseler PA, Cha S, Hwang JH, Cinque P, Cyster JG, Lowell C (2013) CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121:4740–4748. https://doi.org/10.1182/blood-2013-01-476333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schymick JC, Yang Y, Andersen PM, Vonsattel JP, Greenway M, Momeni P, Elder J, Chiò A, Restagno G, Robberecht W, Dahlberg C, Mukherjee O, Goate A, Graff-Radford N, Caselli RJ, Hutton M, Gass J, Cannon A, Rademakers R, Singleton AB, Hardiman O, Rothstein J, Hardy J, Traynor BJ (2007) Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. J Neurol Neurosurg Psychiatry 78(7):754–756

    Article  CAS  Google Scholar 

  • Selmy MA, Ibrahim GH, El Serafi TI, Ghobeish AA (2010) Evaluation of urinary proepithelin as a potential biomarker for bladder cancer detection and prognosis in Egyptian patients. Cancer Biomark 7(3):163–170. https://doi.org/10.3233/CBM-2010-0186

    Article  CAS  PubMed  Google Scholar 

  • Serrero G (2003) Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis. Biochem Biophys Res Commun 308:409–413

    Article  CAS  Google Scholar 

  • Serrero G, Ioffe OB (2003) Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. Hum Pathol 34:1148–1154

    Article  CAS  Google Scholar 

  • Serrero G, Hawkins DM, Yue B, Ioffe O, Bejarano P, Phillips JT, Head JF, Elliott RL, Tkaczuk KR, Godwin AK, Weaver J, Kim WE (2012) Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma. Breast Cancer Res 14(1):R26

    Article  CAS  Google Scholar 

  • Sleegers K, Brouwers N, Van Damme P, Engelborghs S, Gijselinck I, van der Zee J, Peeters K, Mattheijssens M, Cruts M, Vandenberghe R, De Deyn PP, Robberecht W, Van Broeckhoven C (2009) Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 65(5):603–609. https://doi.org/10.1002/ana.21621

    Article  CAS  PubMed  Google Scholar 

  • Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, Rossi G, Pareyson D, Mole SE, Staropoli JF, Sims KB, Lewis J, Lin WL, Dickson DW, Dahl HH, Bahlo M, Berkovic SF (2012) Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 90(6):1102–1107. https://doi.org/10.1016/j.ajhg.2012.04.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strehlow F, Bauer S, Martus P, Weller M, Roth P, Schlegel U, Seidel S, Scheibenbogen C, Korfel A, Kreher S (2016) Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma. J Neuro-Oncol 129:165–171. https://doi.org/10.1007/s11060-016-2162-5

    Article  CAS  Google Scholar 

  • Tanaka A, Tsukamoto H, Mitoma H, Kiyohara C, Ueda N, Ayano M, Ohta S, Inoue Y, Arinobu Y, Niiro H, Horiuchi T, Akashi K (2012) Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity. Arthritis Res Ther 14(6):R244. https://doi.org/10.1186/ar4087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332(6028):478–484. https://doi.org/10.1126/science.1199214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tkaczuk KR, Yue B, Zhan M, Tait N, Yarlagadda L, Dai H, Serrero G (2011) Increased circulating level of the survival factor GP88 (progranulin) in the serum of breast cancer patients when compared to healthy subjects. Breast Cancer (Auckl) 5:155–162. https://doi.org/10.4137/BCBCR.S7224

    Article  CAS  Google Scholar 

  • Toh H, Chitramuthu BP, Bennett HP, Bateman A (2011) Structure, function, and mechanism of progranulin; the brain and beyond. J Mol Neurosci 45(3):538–548. https://doi.org/10.1007/s12031-011-9569-4

    Article  CAS  PubMed  Google Scholar 

  • Vercellino M, Grifoni S, Romagnolo A, Masera S, Mattioda A, Trebini C, Chiavazza C, Caligiana L, Capello E, Mancardi GL, Giobbe D, Mutani R, Giordana MT, Cavalla P (2011) Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis. Mult Scler 17(10):1194–1201. https://doi.org/10.1177/1352458511406164

    Article  CAS  PubMed  Google Scholar 

  • Vercellino M, Fenoglio C, Galimberti D, Mattioda A, Chiavazza C, Binello E, Pinessi L, Giobbe D, Scarpini E, Cavalla P (2016) Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis. Mult Scler 22(8):1007–1012. https://doi.org/10.1177/1352458515610646

    Article  CAS  PubMed  Google Scholar 

  • Viaccoz A, Ducray F, Tholance Y, Barcelos GK, Thomas-Maisonneuve L, Ghesquières H, Meyronet D, Quadrio I, Cartalat-Carel S, Louis-Tisserand G, Jouanneau E, Guyotat J, Honnorat J, Perret-Liaudet A (2015) CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma. Neuro-Oncology 17(11):1497–1503. https://doi.org/10.1093/neuonc/nov092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Li G, Yin J, Lin T, Zhang J (2012) Progranulin overexpression predicts overall survival in patients with glioblastoma. Med Oncol 29(4):2423–2431. https://doi.org/10.1007/s12032-011-0131-6

    Article  CAS  PubMed  Google Scholar 

  • Wei Z, Huang Y, Xie N, Ma Q (2015a) Elevated expression of secreted autocrine growth factor progranulin increases cervical cancer growth. Cell Biochem Biophys 71(1):189–193. https://doi.org/10.1007/s12013-014-0183-2

    Article  CAS  PubMed  Google Scholar 

  • Wei D, Wan Q, Li L, Jin H, Liu Y, Wang Y, Zhang G (2015b) MicroRNAs as potential biomarkers for diagnosing cancers of central nervous system: a meta-analysis. Mol Neurobiol 51:1452–1461. https://doi.org/10.1007/s12035-014-8822-6

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Takemura M, Serrero G, Hayashi J, Yue B, Tsuboi A, Kubo H, Mitsuhashi T, Mannami K, Sato M, Matsunami H, Matuo Y, Saito K (2014) Increased serum GP88 (progranulin) concentrations in rheumatoid arthritis. Inflammation 37:1806–1813. https://doi.org/10.1007/s10753-014-9911-4

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Goto N, Takemura M, Yamasuge W, Yabe K, Takami T, Miyazaki T, Takeuchi T, Shiraki M, Shimizu M, Adachi S, Saito K, Shibata Y, Nakamura N, Hara T, Serrero G, Saito K, Tsurumi H (2017) Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas. Clin Chim Acta 473:139–146. https://doi.org/10.1016/j.cca.2017.07.024

    Article  CAS  PubMed  Google Scholar 

  • Yang D, Wang LL, Dong TT, Shen YH, Guo XS, Liu CY, Liu J, Zhang P, Li J, Sun YP (2015) Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways. Am J Cancer Res 5(10):3085–3097

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Li Z, Shen J, Chan MT, Wu WK (2016) Role of microRNAs in primary central nervous system lymphomas. Cell Prolif 49:147–153. https://doi.org/10.1111/cpr.12243

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan

    Akio Kimura & Takayoshi Shimohata

  2. Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

    Masao Takemura

  3. Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan

    Masao Takemura

Authors
  1. Akio Kimura
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  2. Masao Takemura
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  3. Takayoshi Shimohata
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Correspondence to Akio Kimura .

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Editors and Affiliations

  1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Hideaki Hara

  2. Dementia Research Project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Masato Hosokawa

  3. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Shinsuke Nakamura

  4. Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan

    Takayoshi Shimohata

  5. Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Masugi Nishihara

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Kimura, A., Takemura, M., Shimohata, T. (2019). Progranulin as a Potential Biomarker of Central Nervous System Disease. In: Hara, H., Hosokawa, M., Nakamura, S., Shimohata, T., Nishihara, M. (eds) Progranulin and Central Nervous System Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-13-6186-9_2

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