AIMS: Inflammatory bowel diseases and colorectal cancer are serious intestinal disorders with continuously increasing incidence. Many aspects of etiopathogenesis still remain unclear. There is an urgent need to improve early diagnostics and markers indicating the progression of the disease. The aim of our study was to analyze the expression of matrix metalloproteinase-19 (MMP-19), and the receptor for advanced glycation end-products (RAGE) in different cell subpopulations in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) compared to the tissue in the vicinity of pathological processes. METHODS: Expression of both markers in epithelium, macrophages and vessels were evaluated in IBD and CRC groups. They were detected using immunohistochemistry in paraffin sections. RESULTS: There were significant differences between the expression of MMP-19 on macrophages and vessels among healthy and cancer tissues. In both, macrophages and vessels were significantly lower levels in cancer tissues. The expression of MMP-19 on vessels was also significantly different between peritumoral and cancer tissues (higher levels in peritumoral tissue). RAGE expression in macrophages was significantly different between healthy and cancer tissues and between peritumoral and cancer tissues. There was significantly lower expression in cancer tissues than in healthy and peritumoral tissues. Expression of RAGE in vessels was significantly different just in the comparison of healthy and peritumoral tissues (higher levels in healthy tissues). CONCLUSION: Both markers seem to be promising potential auxiliary markers in IBD and CRC diagnostics. They can also improve evaluation of disease progression.

Department of Pathology

Department of Pathology and Molecular Medicine

Department of Psychology Faculty of Arts Charles University Prague Prague Czech Republic

Department of Surgery 1st Faculty of Medicine Charles University Prague and University Hospital Bulovka Prague Czech Republic

Zobrazit více v PubMed

Cervinková M, Horák P, Kanchev I, Matěj R, Fanta J, Sequens R, Kašpárek P, Sarnová L, Turečková J, Sedláček R. Differential expression and processing of matrix metalloproteinase 19 marks progression of gastrointestinal diseases. Folia Biol 2014;60(3):113-22.

Atkinson SJ, Ward RV, Reynolds JJ, Murphy G. Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases. Biochem J 1992;288 (Pt 2):605-11. PubMed DOI

Murphy G, Knäuper V, Cowell S, Hembry R, Stanton H, Butler G, Freije J, Pendás AM, López-Otín C. Evaluation of some newer matrix metalloproteinases. Ann N Y Acad Sci 1999;878:25-39. PubMed DOI

Cui N, Hu M, Khalil RA. Biochemical and Biological Attributes of Matrix Metalloproteinases. Prog Mol Biol Transl Sci 2017;147:1-73. PubMed DOI

Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol Aspects Med 2008;29(5):290-308. PubMed DOI

Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, Mei Q, Wang Z. Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 2012;44(11):633-41. PubMed DOI

Pendás AM, Folgueras AR, Llano E, Caterina J, Frerard F, Rodríguez F, Astudillo A, Noël A, Birkedal-Hansen H, López-Otín C. Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19 deficient mice. Mol Cell Biol 2004;24(12):5304-13. DOI

Jost M, Folgueras AR, Frérart F, Pendas AM, Blacher S, Houard X, Berndt S, Munaut C, Cataldo D, Alvarez J, Melen-Lamalle L, Foidart JM, López-Otín C, Noël A. Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice. Cancer Res 2006;66(10):5234-41. PubMed DOI

Brauer R, Beck IM, Roderfeld M, Roeb E, Sedlacek R. Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen. BMC Biochem 2011;12:38. PubMed DOI

Chan KC, Ko JM, Lung HL, Sedlacek R, Zhang ZF, Luo DZ, Feng ZB, Chen S, Chen H, Chan KW, Tsao SW, Chua DT, Zabarovsky ER, Stanbridge EJ, Lung ML. Catalytic activity of Matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma. Int J Cancer 2011;129(8):1826-37. PubMed DOI

Alkim C, Alkim H, Koksal AR, Boga S, Sen I. Angiogenesis in Inflammatory Bowel Disease. Int J Inflam 2015;2015:970890. PubMed DOI

Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91(10):3527-61.

Fonseca CG, Barbacena P, Franco CA. Endothelial cells on the move: dynamics in vascular morphogenesis and disease. Vasc Biol 2020;2(1):H29-H43. DOI

Hatoum OA, Heidemann J, Binion DG. The intestinal microvasculature as a therapeutic target in inflammatory bowel disease. Ann N Y Acad Sci 2006;1072:78-97. DOI

Azizian-Farsani F, Abedpoor N, Hasan Sheikhha M, Gure AO, Nasr-Esfahani MH, Ghaedi K. Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development. Front Oncol 2020;10:552283. DOI

Hegab Z, Gibbons S, Neyses L, Mamas MA. Role of advanced glycation end products in cardiovascular disease. World J Cardiol 2012;4(4):90-102. DOI

Ramasamy R, Yan SF, Schmidt AM. Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids 2012;42(4):1151-61. PubMed DOI

Akirav EM, Preston-Hurlburt P, Garyu J, Henegariu O, Clynes R, Schmidt AM, Herold KC. RAGE expression in human T cells: a link between environmental factors and adaptive immune responses. PLoS One 2012;7(4):e34698. PubMed DOI

Maillard-Lefebvre H, Boulanger E, Daroux M, Gaxatte C, Hudson BI, Lambert M. Soluble receptor for advanced glycation end products: a new biomarker in diagnosis and prognosis of chronic inflammatory diseases. Rheumatology 2009;48(10):1190-6. PubMed DOI

Remmele W, Stegner HE. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe 1987;8(3):138-40. PubMed