An Investigation into KLK5, KLK6 and KLK7 Expressions in Intracranial Tumors

Yıl 2020, , 272 - 277, 30.09.2020

Gamze Turna , Nedret Kılıc Gokhan Kurt Fikret Dogulu Necdet Cevıker

https://doi.org/10.34087/cbusbed.673053

Cited By: 1

Öz

Aim: Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases which consists of 15 genes located on the 19th (19q13.3-4) chromosome. Previous studies have shown that kallikrein-related peptidases (KLKs) associated with a variety of cancer types. However, few studies have investigated the role of KLKs in diagnosis and prognosis in intracranial tumors. Therefore, this study aimed to determine expression level changes of KLK5, KLK6 and KLK7 in intracranial tumors.
Materials and methods: Meningioma grade I (n=15) and glioblastoma multiforme (n=15) tumor samples were examined for KLK5, KLK6 and KLK7 mRNA gene expression using reverse transcriptase polymerase chain reaction (RT-PCR). Their protein expression were determined using Western blotting.
Results: KLK5 and KLK7 mRNAs and proteins are expressed more frequently in meningioma group whereas KLK6 mRNA and proteins are expressed more frequently in glioblastoma group.
Conclusion: To conclude, when meningioma and glioblastoma groups were compared, it was found that there were differences in mRNA and protein expression levels of KLK5, KLK6 and KLK7. These genes may have a potential as a new biomarker for diagnosis in intracranial tumors.

Anahtar Kelimeler

Kallikrein-related peptidases 5, kallikrein-related peptidases 6, kallikrein-related peptidases 7, meningioma, glioblastoma

Destekleyen Kurum

Gazi University Scientific Research Projects

Proje Numarası

01/2010-106

Teşekkür

We thank to Assoc. Prof. Dr. Sevin Guney and Yasemin Isik Koc, M.Sc. for their valuable support. This research was supported by Gazi University Scientific Research Projects No. 01/2010-106.

İntrakranial Tümörlerde KLK5, KLK6 ve KLK7 Ekspresyonlarının Araştırılması

Öz

Amaç: 19. kromozom (19q13.3-4) üzerinde bulunan 15 genden oluşan kallikrein ilişkili peptidazlar (KLK’lar), serin proteazların bir alt grubudur. Daha önce yapılan bazı çalışmalar KLK'ların çeşitli kanser türleriyle ilişkili olduğunu göstermiştir. Bununla birlikte, intrakranial tümörlerde KLK'ların tanı ve prognozdaki rolünü araştıran az sayıda çalışma bulunmaktadır. Bu nedenle, bu çalışmada intrakranial tümörlerde KLK5, KLK6 ve KLK7'nin ekspresyon düzeylerindeki değişimlerin belirlenmesi amaçlamıştır.
Materyal ve metod: Menenjiom grade I (n = 15) ve glioblastoma multiforme (n = 15) tümör örneklerinde, KLK5, KLK6 ve KLK7 mRNA ekspresyon düzeyleri ters transkriptaz polimeraz zincir reaksiyonu (RT-PCR) kullanılarak tespit edildi. Protein ekspresyonları ise western blotting yöntemi kullanılarak belirlendi.
Bulgular: KLK5 ve KLK7’nin mRNA ve proteinleri menenjiom grubunda daha sıklıkla ifade edilirken, KLK6’nın mRNA ve proteini glioblastoma grubunda daha sıklıkla ifade edilmektedir.
Sonuç: Menenjiom ve glioblastoma grupları karşılaştırıldığında KLK5, KLK6 ve KLK7 mRNA ve protein ekspresyon düzeylerinde farklılıklar olduğu tespit edilmiştir. Bu genler intrakranial tümörlerin tanısı için yeni bir biyobelirteç olma potansiyeline sahip olabilir.

Anahtar Kelimeler

Kallikrein ilişkili peptidaz 5, kallikrein ilişkili peptidaz 6, kallikrein ilişkili peptidaz 7, menenjiom, glioblastoma

Proje Numarası

01/2010-106

Kaynakça

• 1. Yousef GM, Chang A, Scorilas A, Diamandis EP. Genomic organization of the human kallikrein gene family on chromosome 19q13.3-q13.4. Biochemical and Biophysical Research Communications, 2000; 276: 125-33.
• 2. Lundwall A, Brattsand M. Kallikrein-related peptidases. Cellular and Molecular Life Sciences, 2008; 65: 2019-2038.
• 3. Emami N, Diamandis EP. Human tissue kallikreins: a road under construction. Clinica Chimica Acta, 2007; 381: 78-84.
• 4. Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clinical Chemistry, 2007; 53: 1423-1432.
• 5. Caubet C, Jonca N, Brattsand M, Guerrin M, Bernard D et al. Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. The Journal of Investigative Dermatology, 2004; 122: 1235-44.
• 6. Stefanini AC, da Cunha BR, Henrique T, Tajara EH. Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Processes. Disease Markers, 2015; 2015: 946572.
• 7. Diamandis EP, Scorilas A, Kishi T, Blennow K, Luo LY et al. Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. Clinical Biochemistry, 2004; 37: 230-7.
• 8. Anisowicz A, Sotiropoulou G, Stenman G, Mok SC, Sager R. A novel protease homolog differentially expressed in breast and ovarian cancer. Molecular Medicine, 1996; 2: 624–36.
• 9. Little SP, Dixon EP, Norris F, Buckley W, Becker GW et al. Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer’s disease brain. The Journal of Biological Chemistry, 1997; 272: 25135–42.
• 10. Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y et al. Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochimica et Biophysica Acta, 1997; 1350: 11–4.
• 11. Christodoulou S, Alexopoulou DK, Kontos CK, Scorilas A, Papadopoulos IN. Kallikrein-related peptidase-6 (KLK6) mRNA expression is an independent prognostic tissue biomarker of poor disease-free and overall survival in colorectal adenocarcinoma. Tumour Biology, 2014; 35: 4673-85.
• 12. Kim JJ, Kim JT, Yoon HR, Kang MA, Kim JH et al. Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer. Tumour Biology, 2012; 33: 731-8.
• 13. White NM, Mathews M, Yousef GM, Prizada A, Popadiuk C et al. KLK6 and KLK13 predict tumor recurrence in epithelial ovarian carcinoma. British Journal of Cancer, 2009; 101: 1107-13.
• 14. Yousef GM, Scorilas A, Magklara A, Soosaipillai A, Diamandis EP. The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family-genomic characterization, mapping, tissue expression and hormonal regulation. Gene, 2000; 254: 119-128.
• 15. Hansson L, Strömqvist M, Bäckman A, Wallbrandt P, Carlstein A et al. Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase. The Journal of Biological Chemistry, 1994; 269: 19420-19426.
• 16. Brattsand M, Egelrud T. Purification, molecular cloning, and expression of a human stratum corneum trypsin-like serine protease with possible function in desquamation. The Journal of Biological Chemistry, 1999; 274: 30033-30040.
• 17. Yamasaki K, Schauber J, Coda A, Lin H, Dorschner RA et al. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB Journal, 2006; 20: 2068-2080.
• 18. Yousef GM, Obiezu CV, Jung K, Stephan C, Scorilas A et al. Differential expression of Kallikrein gene 5 in cancerous and normal testicular tissues. Urology, 2002; 60: 714-718.
• 19. Talieri M, Devetzi M, Scorilas A, Prezas P, Ardavanis A et al. Evaluation of kallikrein-related peptidase 5 expression and its significance for breast cancer patients: association with kallikrein-related peptidase 7 expression. Anticancer Research, 2011; 31: 3093-100.
• 20. Li W, Zhao Y, Ren L, Wu X. Serum human kallikrein 7 represents a new marker for cervical cancer. Medical Oncology, 2014; 31: 208.
• 21. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer Journal of Clinicians, 2016; 66: 7-30.
• 22. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro-Oncology, 2015; 17 Suppl 4: iv1-iv62.
• 23. Marosi C, Hassler M, Roessler K, Reni M, Sant M et al. Meningioma. Critical Reviews in Oncology/ Hematology, 2008; 67: 153-171.
• 24. Bi WL, Zhang M, Wu WW, Mei Y, Dunn IF. Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications. Frontiers in Surgery, 2016; 3:40.
• 25. Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiology, Biomarkers & Prevention, 2014; 23: 1985-96.
• 26. Wen PY, Kesari S. Malignant gliomas in adults. The New England Journal of Medicine, 2008; 359: 492-507.
• 27. Kalinska M, Meyer-Hoffert U, Kantyka T, Potempa J. Kallikreins-The melting pot of activity and function. Biochimie, 2016; 122: 270-82.
• 28. Kim H, Scorilas A, Katsaros D, Yousef GM, Massobrio M et al. Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer. British Journal of Cancer, 2001; 84: 643-650.
• 29. Emami N, Diamandis EP. Utility of kallikrein-related peptidases (KLKs) as cancer biomarkers. Clinical Chemistry, 2008; 54: 1600-7.
• 30. Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G et al. Characterization of the enzymatic activity of human kallikrein 6: autoactivation, substrate specificity, and regulation by inhibitors. Biochemical and Biophysical Research Communications, 2003; 307: 948-955.
• 31. Nagahara H, Mimori K, Utsunomiya T, Barnard GF, Ohira M et al. Clinicopathologic and biological significance of KLK6 overexpression in human gastric cancer. Clinical Cancer Research, 2005; 11: 6800-6806.
• 32. Pampalakis G, Prosnikli E, Agalioti T, Vlahou A, Zoumpourlis V et al. A tumor-protective role for human kallikrein related peptidase 6 in breast cancer mediated by inhibition of epithelial-to-mesenchymal transition. Cancer Research, 2009; 69: 3779-3787.
• 33. Strojnik T, Kavalar R, Zajc I, Diamandis EP, Oikonomopoulou K et al. Prognostic impact of CD68 and kallikrein 6 in human glioma. Anticancer Research, 2009; 29: 3269-3279.
• 34. Talieri M, Zoma M, Devetzi M, Scorilas A, Ardavanis A. Kallikrein-related peptidase 6 (KLK6) gene expression in intracranial tumors. Tumour Biology, 2012; 33: 1375-1383.
• 35. Drucker KL, Paulsen AR, Giannini C, Decker PA, Blaber SI et al. Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma. Neuro-Oncology, 2013; 15: 305-318.
• 36. Johnson SK, Ramani VC, Hennings L, Haun RS. Kallikrein 7 enhances pancreatic cancer cell invasion by shedding E-cadherin. Cancer, 2007; 109: 1811-1820.
• 37. Mo L, Zhang J, Shi J, Xuan Q, Yang X et al. Human kallikrein 7 induces epithelial-mesenchymal transition-like changes in prostate carcinoma cells: a role in prostate cancer invasion and progression. Anticancer Research, 2010; 30: 3413-3420.
• 38. Prezas P, Scorilas A, Yfanti C, Viktorov P, Agnanti N et al. The role of human tissue kallikreins 7 and 8 in intracranial malignancies. Biological Chemistry, 2006; 387: 1607-1612.
• 39. Drucker KL, Giannini C, Decker PA, Diamandis EP, Scarisbrick IA. Prognostic significance of multiple kallikreins in high-grade astrocytoma. BMC Cancer, 2015; 15: 565.