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Evaluation of matrix metalloproteinase-2 and -9 in the cerebrospinal fluid of dogs with intracranial tumors

Christopher L. MarianiComparative Neuroimmunology and Neurooncology Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Lindsay B. BoozerComparative Neuroimmunology and Neurooncology Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Alicia M. BraxtonComparative Neuroimmunology and Neurooncology Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Simon R. PlattDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Karen M. VernauDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

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John J. McDonnellDepartment of Clinical Studies-Philadelphia, College of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Julien GuevarGarston Veterinary Group, Ulster Lodge, Plants Green, Warminster, Wiltshire, BA12 9BG, England.

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Abstract

Objective—To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors.

Sample—CSF from 55 dogs with intracranial tumors and 37 control dogs.

Procedures—Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated.

Results—Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration.

Conclusions and Clinical Relevance—Latent MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.

Abstract

Objective—To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors.

Sample—CSF from 55 dogs with intracranial tumors and 37 control dogs.

Procedures—Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated.

Results—Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration.

Conclusions and Clinical Relevance—Latent MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.

Contributor Notes

Dr. Boozer's present address is Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

Dr. Guevar's present address is Millenium Veterinary Practice, Millenium Way, Braintree, Essex, CM7 3GX, England.

Supported by the American College of Veterinary Internal Medicine Foundation (grant No. 08-24D) and by funds made available to Dr. Mariani by the Department of Clinical Sciences and the College of Veterinary Medicine, North Carolina State University.

Presented in part as a poster at the American College of Veterinary Internal Medicine 28th Annual Forum, Anaheim, Calif, June 2010.

The authors thank Dr. Marlene Hauck for providing supernatant samples from cultured canine neoplastic cell lines.

Address correspondence to Dr. Mariani (clmarian@ncsu.edu).