Co-expression of TIMP-1 and its cell surface binding partner CD63 in glioblastomas

被引：36

作者：

Aaberg-Jessen, Charlotte ^{[1
,2
]}

Sorensen, Mia D. ^{[1
,3
]}

Matos, Ana L. S. A. ^{[4
]}

Moreira, Jose M. ^{[4
]}

Brunner, Nils ^{[4
]}

Knudsen, Arnon ^{[1
,3
]}

Kristensen, Bjarne W. ^{[1
,3
]}

机构：

[1] Odense Univ Hosp, Dept Pathol, JB Winsloews Vej 15, DK-5000 Odense, Denmark

[2] Odense Univ Hosp, Dept Nucl Med, Sdr Blvd 29, DK-5000 Odense, Denmark

[3] Univ Southern Denmark, Dept Clin Res, JB Winsloews Vej 19, DK-5000 Odense, Denmark

[4] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Canc Res Grp, Strandblvd 49, DK-2100 Copenhagen, Denmark

来源：

BMC CANCER | 2018年 / 18卷

关键词：

TIMP; CD63; LAMP-3; Glioblastoma; Glioma; Astrocytoma; Microglia; Extracellular matrix; Prognosis; Biomarker; PLASMA TISSUE INHIBITOR; STEM-CELL; COLORECTAL-CANCER; POOR-PROGNOSIS; SERUM TIMP-1; EXTRACELLULAR VESICLES; SURVIVAL OUTCOMES; BREAST-CARCINOMA; GRADE GLIOMAS; GENE ONTOLOGY;

D O I：

10.1186/s12885-018-4179-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: We have previously identified tissue inhibitor of metalloproteinases-1 (TIMP-1) as a prognostic marker in glioblastomas. TIMP-1 has been associated with chemotherapy resistance, and CD63, a known TIMP-1-binding protein, has been suggested to be responsible for this effect. The aim of this study was to assess CD63 expression in astrocytomas focusing on the prognostic potential of CD63 alone and in combination with TIMP-1. Methods: CD63 expression was investigated immunohistochemically in a cohort of 111 astrocytomas and correlated to tumor grade and overall survival by semi-quantitative scoring. CD63 expression in tumor-associated microglia/macrophages was examined by double-immunofluorescence with ionized calcium-binding adapter molecule 1 (Iba1). The association between CD63 and TIMP-1 was investigated using previously obtained TIMP-1 data from our astrocytoma cohort. Cellular co-expression of TIMP-1 and CD63 as well as TIMP-1 and the tumor stem cell-related markers CD133 and Sox2 was investigated with immunofluorescence. TIMP-1 and CD63 protein interaction was detected by an oligonucleotide-based proximity ligation assay and verified using co-immunoprecipitation. Results: The expression of CD63 was widely distributed in astrocytomas with a significantly increased level in glioblastomas. CD63 levels did not significantly correlate with patient survival at a protein level, and CD63 did not augment the prognostic significance of TIMP-1. Up to 38% of the CD63+ cells expressed Iba1; however, Iba1 did not appear to impact the prognostic value of CD63. A significant correlation was found between TIMP-1 and CD63, and the TIMP-1 and CD63 proteins were co-expressed at the cellular level and located in close molecular proximity, suggesting that TIMP-1 and CD63 could be co-players in glioblastomas. Some TIMP-1+ cells expressed CD133 and Sox2. Conclusion: The present study suggests that CD63 is highly expressed in glioblastomas and that TIMP-1 and CD63 interact. CD63 does not add to the prognostic value of TIMP-1. Co-expression of TIMP-1 and stem cell markers as well as the wide expression of CD63 might suggest a role for TIMP-1 and CD63 in glioblastoma stemness.

引用

页数：16

共 87 条

[1]

Aaberg-Jessen C, 2013, INT J CLIN EXP PATHO, V6, P546

[2]

Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival [J].

Aaberg-Jessen, Charlotte ;

Christensen, Karina ;

Offenberg, Hanne ;

Bartels, Annette ;

Dreehsen, Tanja ;

Hansen, Steinbjorn ;

Schroder, Henrik Daa ;

Brunner, Nils ;

Kristensen, Bjarne Winther .

JOURNAL OF NEURO-ONCOLOGY, 2009, 95 (01) :117-128

[3]

Overexpression of CD133 Promotes Drug Resistance in C6 Glioma Cells [J].

Angelastro, James M. ;

Lame, Michael W. .

MOLECULAR CANCER RESEARCH, 2010, 8 (08) :1105-1115

[4]

Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[5]

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].

Bao, Shideng ;

Wu, Qiulian ;

McLendon, Roger E. ;

Hao, Yueling ;

Shi, Qing ;

Hjelmeland, Anita B. ;

Dewhirst, Mark W. ;

Bigner, Darell D. ;

Rich, Jeremy N. .

NATURE, 2006, 444 (7120) :756-760

[6]

Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma [J].

Bhat, Krishna P. L. ;

Balasubramaniyan, Veerakumar ;

Vaillant, Brian ;

Ezhilarasan, Ravesanker ;

Hummelink, Karlijn ;

Hollingsworth, Faith ;

Wani, Khalida ;

Heathcock, Lindsey ;

James, Johanna D. ;

Goodman, Lindsey D. ;

Conroy, Siobhan ;

Long, Lihong ;

Lelic, Nina ;

Wang, Suzhen ;

Gumin, Joy ;

Raj, Divya ;

Kodama, Yoshinori ;

Raghunathan, Aditya ;

Olar, Adriana ;

Joshi, Kaushal ;

Pelloski, Christopher E. ;

Heimberger, Amy ;

Kim, Se Hoon ;

Cahill, Daniel P. ;

Rao, Ganesh ;

Den Dunnen, Wilfred F. A. ;

Boddeke, Hendrikus W. G. M. ;

Phillips, Heidi S. ;

Nakano, Ichiro ;

Lang, Frederick F. ;

Colman, Howard ;

Sulman, Erik P. ;

Aldape, Kenneth .

CANCER CELL, 2013, 24 (03) :331-346

[7]

Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: A prospective validation study [J].

Birgisson, Helgi ;

Nielsen, Hans J. ;

Christensen, Ib Jarle ;

Glimelius, Bengt ;

Brunner, Nils .

EUROPEAN JOURNAL OF CANCER, 2010, 46 (18) :3323-3331

[8]

Expansion of the Gene Ontology knowledgebase and resources [J].

Carbon, S. ;

Dietze, H. ;

Lewis, S. E. ;

Mungall, C. J. ;

Munoz-Torres, M. C. ;

Basu, S. ;

Chisholm, R. L. ;

Dodson, R. J. ;

Fey, P. ;

Thomas, P. D. ;

Mi, H. ;

Muruganujan, A. ;

Huang, X. ;

Poudel, S. ;

Hu, J. C. ;

Aleksander, S. A. ;

McIntosh, B. K. ;

Renfro, D. P. ;

Siegele, D. A. ;

Antonazzo, G. ;

Attrill, H. ;

Brown, N. H. ;

Marygold, S. J. ;

McQuilton, P. ;

Ponting, L. ;

Millburn, G. H. ;

Rey, A. J. ;

Stefancsik, R. ;

Tweedie, S. ;

Falls, K. ;

Schroeder, A. J. ;

Courtot, M. ;

Osumi-Sutherland, D. ;

Parkinson, H. ;

Roncaglia, P. ;

Lovering, R. C. ;

Foulger, R. E. ;

Huntley, R. P. ;

Denny, P. ;

Campbell, N. H. ;

Kramarz, B. ;

Patel, S. ;

Buxton, J. L. ;

Umrao, Z. ;

Deng, A. T. ;

Alrohaif, H. ;

Mitchell, K. ;

Ratnaraj, F. ;

Omer, W. ;

Rodriguez-Lopez, M. .

NUCLEIC ACIDS RESEARCH, 2017, 45 (D1) :D331-D338

[9]

Podoplanin is a component of extracellular vesicles that reprograms cell-derived exosomal proteins and modulates lymphatic vessel formation [J].

Carrasco-Ramirez, Patricia ;

Greening, David W. ;

Andres, German ;

Gopal, Shashi K. ;

Martin-Villar, Ester ;

Renart, Jaime ;

Simpson, Richard J. ;

Quintanilla, Miguel .

ONCOTARGET, 2016, 7 (13) :16070-16089

[10]

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma [J].

Ceccarelli, Michele ;

Barthel, Floris P. ;

Malta, Tathiane M. ;

Sabedot, Thais S. ;

Salama, Sofie R. ;

Murray, Bradley A. ;

Morozova, Olena ;

Newton, Yulia ;

Radenbaugh, Amie ;

Pagnotta, Stefano M. ;

Anjum, Samreen ;

Wang, Jiguang ;

Manyam, Ganiraju ;

Zoppoli, Pietro ;

Ling, Shiyun ;

Rao, Arjun A. ;

Grifford, Mia ;

Cherniack, Andrew D. ;

Zhang, Hailei ;

Poisson, Laila ;

Carlotti, Carlos Gilberto, Jr. ;

Tirapelli, Daniela Pretti da Cunha ;

Rao, Arvind ;

Mikkelsen, Tom ;

Lau, Ching C. ;

Yung, W. K. Alfred ;

Rabadan, Raul ;

Huse, Jason ;

Brat, Daniel J. ;

Lehman, Norman L. ;

Barnholtz-Sloan, Jill S. ;

Zheng, Siyuan ;

Hess, Kenneth ;

Rao, Ganesh ;

Meyerson, Matthew ;

Beroukhim, Rameen ;

Cooper, Lee ;

Akbani, Rehan ;

Wrensch, Margaret ;

Haussler, David ;

Aldape, Kenneth D. ;

Laird, Peter W. ;

Gutmann, David H. ;

Noushmehr, Houtan ;

Iavarone, Antonio ;

Verhaak, Roel G. W. .

CELL, 2016, 164 (03) :550-563

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