Melatonergic system-based two-gene index is prognostic in human gliomas
Carregando...
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
KINKER, Gabriela S.
CARVALHO-SOUSA, Claudia E.
MUXEL, Sandra M.
MARKUS, Regina P.
FERNANDES, Pedro A.
Citação
JOURNAL OF PINEAL RESEARCH, v.60, n.1, p.84-94, 2016
Resumo
Gliomas, the most common primary brain tumors in adults, are classified into four malignancy grades according to morphological features. Recent studies have shown that melatonin treatment induces cytotoxicity in glioma-initiating cells and reduces the invasion and migration of glioma cell lines, inhibiting the nuclear factor kappa B (NF kappa B) oncopathway. Given that C6 rat glioma cells produce melatonin, we investigated the correlation between the capacity of gliomas to synthesize/metabolize melatonin and their overall malignancy. We first characterized the melatonergic system of human gliomas cell lines with different grades of aggressiveness (HOG, T98G, and U87MG) and demonstrated that glioma-synthesized melatonin exerts an autocrine antiproliferative effect. Accordingly, the sensitivity to exogenous melatonin was higher for the most aggressive cell line, U87MG, which synthesized/accumulated less melatonin. Using The Cancer Genome Atlas RNAseq data of 351 glioma patients, we designed a predictive model of the content of melatonin in the tumor microenvironment, the ASMT:CYP1B1 index, combining the gene expression levels of melatonin synthesis and metabolism enzymes. The ASMT: CYP1B1 index negatively correlated with tumor grade, as well as with the expression of pro-proliferation and anti-apoptotic NF kappa B target genes. More importantly, the index was a grade-and histological type-independent prognostic factor. Even when considering only high-grade glioma patients, a low ASMT: CYP1B1 value, which suggests decreased melatonin and enhanced aggressiveness, was strongly associated with poor survival. Overall, our data reveal the prognostic value of the melatonergic system of gliomas and provide insights into the therapeutic role of melatonin.
Palavras-chave
ASMT, brain tumor, CYP1B1, melatonin, molecular markers
Referências
- Acuna-Castroviejo D, 2014, CELL MOL LIFE SCI, V71, P2997, DOI 10.1007/s00018-014-1579-2
- Louis DN, 2007, ACTA NEUROPATHOL, V114, P97, DOI 10.1007/s00401-007-0243-4
- Anderson G, 2014, CNS NEUROL DISORD-DR, V13, P817
- BERNARD M, 1995, BRAIN RES, V696, P37, DOI 10.1016/0006-8993(95)00651-6
- Barrett P, 2012, J PINEAL RES, V52, P376, DOI 10.1111/j.1600-079X.2011.00963.x
- Liu YJ, 2007, J PINEAL RES, V43, P232, DOI 10.1111/j.1600-079X.2007.00466.x
- Ma XC, 2005, DRUG METAB DISPOS, V33, P489, DOI 10.1124/dmd.104.002410
- Gribben JG, 2005, CLIN CANCER RES, V11, P4430, DOI 10.1158/1078-0432.CCR-04-2111
- Jiang YW, 2012, UPSALA J MED SCI, V117, P113, DOI 10.3109/03009734.2012.658976
- Pahl HL, 1999, ONCOGENE, V18, P6853, DOI 10.1038/sj.onc.1203239
- Karin M, 2002, NAT REV CANCER, V2, P301, DOI 10.1038/nrc780
- Martin V, 2013, BRIT J CANCER, V108, P2005, DOI 10.1038/bjc.2013.188
- Kadekaro AL, 2004, J PINEAL RES, V36, P204, DOI 10.1111/j.1600-079X.2004.00119.x
- Johnson DR, 2012, J NEURO-ONCOL, V107, P359, DOI 10.1007/s11060-011-0749-4
- Kim S, 2002, MOL CANCER THER, V1, P1229
- Jablonska K, 2013, J PINEAL RES, V54, P334, DOI 10.1111/jpi.12032
- Gilmore TD, 2006, ONCOGENE, V25, P6680, DOI 10.1038/sj.onc.1209954
- Liu TC, 2005, J PINEAL RES, V39, P91, DOI 10.1111/j.1600-079X.2005.00223.x
- Verhaak RGW, 2010, CANCER CELL, V17, P98, DOI 10.1016/j.ccr.2009.12.020
- Subramanian A, 2005, P NATL ACAD SCI USA, V102, P15545, DOI 10.1073/pnas.0506580102
- Froklage FE, 2014, J NEURO-ONCOL, V116, P387, DOI 10.1007/s11060-013-1310-4
- Baud V, 2009, NAT REV DRUG DISCOV, V8, P33, DOI 10.1038/nrd2781
- Xi SC, 2000, J PINEAL RES, V29, P172, DOI 10.1034/j.1600-079X.2000.d01-64.x
- Murray GI, 1997, CANCER RES, V57, P3026
- Maecker B, 2003, BLOOD, V102, P3287, DOI 10.1182/blood-2003-05-1374
- Pinato L, 2015, BRAIN STRUCT FUNCT, V220, P827, DOI 10.1007/s00429-013-0686-4
- Venegas C, 2012, J PINEAL RES, V52, P217, DOI 10.1111/j.1600-079X.2011.00931.x
- van den Bent MJ, 2010, ACTA NEUROPATHOL, V120, P297, DOI 10.1007/s00401-010-0725-7
- DUBOISDALCQ M, 1986, J CELL BIOL, V102, P384, DOI 10.1083/jcb.102.2.384
- Yuan L, 2002, MOL CELL ENDOCRINOL, V192, P147, DOI 10.1016/S0303-7207(02)00029-1
- Huse JT, 2010, NAT REV CANCER, V10, P319, DOI 10.1038/nrc2818
- Wang HM, 2004, LAB INVEST, V84, P941, DOI 10.1038/labinvest.3700123
- Hardeland R, 2011, PROG NEUROBIOL, V93, P350, DOI 10.1016/j.pneurobio.2010.12.004
- Mediavilla MD, 2010, CURR MED CHEM, V17, P4462
- Wang JT, 2012, J PINEAL RES, V53, P180, DOI 10.1111/j.1600-079X.2012.00985.x
- Ma XJ, 2004, CANCER CELL, V5, P607, DOI 10.1016/j.ccr.2004.05.015
- Reiter RJ, 2014, BRAIN STRUCT FUNCT, V219, P1873, DOI 10.1007/s00429-014-0719-7
- Luby TM, 2004, CLIN IMMUNOL, V112, P45, DOI 10.1016/j.clim.2004.04.002
- Korkolopoulou P, 2008, HUM PATHOL, V39, P1143, DOI 10.1016/j.humpath.2008.01.020
- FOGH J, 1977, J NATL CANCER I, V59, P221
- Phillips HS, 2006, CANCER CELL, V9, P157, DOI 10.1016/j.ccr.2006.02.019
- Hardeland R, 2012, J PINEAL RES, V52, P139, DOI 10.1111/j.1600-079X.2011.00934.x
- Barnett JA, 2007, CLIN CANCER RES, V13, P3559, DOI 10.1158/1078-0432.CCR-06-2430
- YOUNG IM, 1985, J CLIN ENDOCR METAB, V60, P114
- Collins A, 2003, CANCER LETT, V189, P49, DOI 10.1016/S0304-3835(02)00502-5
- Simonneaux V, 2003, PHARMACOL REV, V55, P325, DOI 10.1124/pr.55.2.2
- Fukuda T, 2010, J NEUROPATH EXP NEUR, V69, P498, DOI 10.1097/NEN.0b013e3181db7d3c
- Slominski A, 2002, FASEB J, V16, P896, DOI 10.1096/fj.01-0952fje
- Budczies J, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0051862
- Grant SG, 2009, EXPERT REV MOL MED, V11, DOI 10.1017/S1462399409000982
- Han YY, 2011, AM J PHYSIOL-GASTR L, V301, pG623, DOI 10.1152/ajpgi.00118.2011
- LOSCHER W, 2007, CLIN CANCER RES, V13, P1663
- Martin V, 2014, J PINEAL RES, V57, P308, DOI 10.1111/jpi.12170
- Martin V, 2006, CANCER RES, V66, P1081, DOI 10.1158/0008-5472.CAN-05-2354
- Ostrom QT, 2014, NEURO-ONCOLOGY, V16, P1, DOI 10.1093/neuonc/nou223
- Polimeni G, 2014, FRONT BIOSCI-LANDMRK, V19, P429, DOI 10.2741/4217
- Zanotto A, 2011, BIOCHEM PHARMACOL, V81, P412, DOI 10.1016/j.bcp.2010.10.014