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Oulun yliopiston väitöskirjat

MATRIX METALLOPROTEINASE-8 AS A DIAGNOSTIC TOOL FOR THE INFLAMMATORY AND MALIGNANT DISEASES, ACTA UNIVERSITATIS OULUENSIS D Medica 1111

ISBN-13:	978-951-42-9508-9
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Oppiaine:	Lääketiede,farmasia
Painosvuosi:	2011
Sidosasu:	pehmeäkantinen
Sijainti:	Print Tietotalo
Sivumäärä:	130
Tekijät:	PRADHAN-PALIKHE PRATIKSHYA

20.00 €

Matrix metalloproteinases (MMPs) are the zinc-dependent endopeptidases which belong to a largefamily of proteases. MMPs are responsible for degradation and remodeling of extracellular matrixproteins during growth, organogenesis and tissue turnover. Besides their role in physiologicalprocesses, MMPs also influence various pathological processes, i.e., inflammatory diseases andcancers, in which MMPs may ultimately lead to unwanted tissue destruction. One of the mostwidely studied MMPs is MMP-8. MMP-8 was previously thought to be expressed only byneutrophils. Presently, it is evident that MMP-8 can be expressed in a wide range of cells such asmacrophages, plasma cells, T-cells, endothelial cells, smooth muscle cells, oral epithelial cells,fibroblasts etc. MMP-8 has been previously studied in inflammation and malignancies. Highserum MMP-8 concentration is associated with the presence of atherosclerosis and poorcardiovascular disease prognosis, while higher plasma MMP-8 levels protect against lymph nodemetastasis. Certain MMP-8 gene variations can alter promoter activity and subsequent geneexpression. MMP-8 gene variation influences obstetrical outcomes, and lung and breast cancerprognosis. For our study, we hypothesized that systemic levels of MMP-8 correlate with its geneticvariations and appear as novel risk markers for disease. We aimed to address the potential role of MMPs and their regulators with a special focus onMMP-8 in distinct sets of inflammatory and malignant diseases, i.e. arterial diseases, and head andneck squamous cell cancer (HNSCC). We demonstrated that the combination of high serumMMP-8 and low myeloperoxidase (MPO) levels is an important risk marker for arterial disease.Further, we demonstrated that MMP-8 gene variation is protective against arterial diseases.Interestingly, we were able to demonstrate an association between MMP-8 gene variation andserum MMP-8 concentration in a healthy population. On the other hand, we showed that plasmatissue inhibitor of matrix metalloproteinases (TIMP-1) concentration is associated with survival inHNSCC patients and TIMP-1 genotype is associated with plasma TIMP-1 levels in women only. Collectively, our study showed that serum MMP-8 levels can be used as an important riskmarker in arterial disease and TIMP-1 levels in HNSCC patients. Based on our results, thehypothesis raised has been widely confirmed. Additionally, our study has warranted the need forfurther investigation involving a larger number of patients. If our results are replicable, serumMMP-8 and plasma TIMP-1 could be used to develop diagnostic tools as well as treatmentregimes in clinics.

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