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World J Gastroenterol. Oct 7, 2014; 20(37): 13246-13257
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13246
Impact of proteolytic enzymes in colorectal cancer development and progression
László Herszényi, Loránd Barabás, István Hritz, Gábor István, Zsolt Tulassay
László Herszényi, Zsolt Tulassay, 2nd Department of Medicine, Semmelweis University, H-1088 Budapest, Hungary
Loránd Barabás, Gábor István, 2nd Department of Surgery, Semmelweis University, H-1024 Budapest, Hungary
István Hritz, 1st Department of Medicine, Fejér Megyei Szent György University Teaching Hospital, H-8000 Székesfehérvár, Hungary
Author contributions: Herszényi L, Barabás L, Hritz I, István G and Tulassay Z contributed equally to this work; Herszényi L, Barabás L and Hritz I wrote the paper; István G contributed to the revision of the manuscript; Tulassay Z critically revised the manuscript for important intellectual content.
Correspondence to: László Herszényi, MD, DSc, 2nd Department of Medicine, Semmelweis University, Szentkirályi str. 46, H-1088 Budapest, Hungary. herszenyi.laszlo@med.semmelweis-univ.hu
Telephone: +36-1-2660926  Fax: +36-1-2660816
Received: October 26, 2013
Revised: January 26, 2014
Accepted: May 23, 2014
Published online: October 7, 2014
Processing time: 345 Days and 20.9 Hours
Abstract

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.

Keywords: Proteinase; Cathepsin; Plasminogen activator; Matrix metalloproteinase; Colorectal cancer; Adenoma; Invasion; Metastasis; Biomarker; Prognosis

Core tip: Tumor invasion and metastasis is a highly complex phenomenon. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, in colorectal cancer (CRC) invasion and metastasis, as well as in the malignant transformation of colorectal adenomas. Tissue and serum-plasma antigen concentrations of proteinases are strong prognostic factors in CRC and may have tumor marker impact for early diagnosis. Proteolytic enzymes may serve as potential target molecules for CRC therapy. Their use in combination with established chemotherapeutic strategies might have the potential to become a valuable oncological treatment modality.