The Role of Inflammation and Proteinases in Tumor Progression

Herszényi, László; Lakatos, Gábor; Hritz, István; Varga, Mária Zsófia; Cierny, Gabriel; Tulassay, Zsolt

doi:10.1159/000336914

Cited by 32 publications

(26 citation statements)

References 142 publications

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“…Although the pathogenic impact of chronic inflammation has been proposed in tumor initiation and progression, the exact mechanism of this connection is still not completely elucidated [9]. It has been proposed that persistent inflammation is an indispensable prerequisite for the development of CRC: chronic inflammation and the increased turnover of epithelial cells contribute to cellular damage and molecular changes that transform inflamed mucosa to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and finally CRC.…”

Section: The Role Of Inflammationmentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

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Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.

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Section: The Role Of Inflammationmentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

Self Cite

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“…It has been shown that cancer metastasis is a complex series of sequential processes: the initial transforming event; proliferation of transformed cells; the ability of tumor cells to avoid destruction by immune-response; nutrition supply to the tumor mass; local invasion and destruction of extracellular matrix components (ECM); migration of tumor cells; penetration of tumor cells through the blood vessel wall; embolization of tumor cells and adhesion to distant organs; arrest of cancer cells in the lumen of small blood vessels and lymphatics; reverse penetration of blood vessels and formation of distant metastases [5–10]. …”

Section: Events During Tumor Invasion and Metastasismentioning

confidence: 99%

“…Chemotactic factors can influence the direction of migration. Invasion of ECM is accomplished by cyclic reverberation of these three steps [7,10–15]. …”

Section: Events During Tumor Invasion and Metastasismentioning

confidence: 99%

The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer

Herszényi

Hritz

Lakatos

et al. 2012

IJMS

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138

137

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Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.

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“…There is evidence supporting the hypothesis that inflammation participates in providing conditions that lead to cancer [26,27], and there are well known associations between inflammatory processes and cancer, such as inflammatory bowel disease and colorectal cancer [28,29], viral hepatitis B and C or alcoholic liver cirrhosis and hepatocarcinoma [30], chronic reflux esophagitis resulting in Barrett's esophagus and esophageal carcinoma [29], cervical infection by human papillomavirus and cervical cancer, prostatitis and prostate cancer, pancreatitis and pancreatic cancer, or gastric infection from Helicobacter pylori and gastric cancer [31,32].…”

Section: Mmps and Timps In Disease And Cancermentioning

confidence: 79%

Clinical Relevance of Matrix Metalloproteases and their Inhibitors in Breast Cancer

2013

J Carcinog Mutagen

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Degradation of the stromal connective tissue and basement membrane components are key elements in tumor invasion and metastasis. Some components, particularly the interstitial collagens, are very resistant to proteolytic attacks and can be degraded by specific proteinases like Matrix Metalloproteinases (MMPs). MMPs can also impact on tumor cell behavior in vivo as a consequence of their ability to cleave growth factors, cell surface receptors, cell adhesion molecules, or chemokines/cytokines, and for stimulating angiogenesis. Different molecular expression profiles of MMPs and their inhibitors (TIMPs) have been associated with the main steps in breast cancer progression, such as creating a potential invasive phenotype in Ductal Carcinoma in situ (DCIS), favoring the hematogenous dissemination, and enabling the metastatic progression across the axillary lymphatic system. These associations have clinical interests, as they can contribute to a better characterization of early breast carcinomas (which differ in their both biological and clinical behavior), evaluate microinvasion in resection specimens of breast tumors, provide a more precise prognostic, and predict the tumoral status of non-sentinel lymph nodes in breast cancer. It is also especially remarkable the evidences indicating that MMPs and TIMPs expression in individual cell populations from tumor stroma, such as mononuclear inflammatory cells (MICs) and fibroblast, clearly impacts on the clinical outcome of breast cancer patients. There are several factors linking inflammation, MMP activity and breast cancer. This knowledge will be useful to develop novel therapies and prevention strategies targeting critical components.

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The Role of Inflammation and Proteinases in Tumor Progression

Cited by 32 publications

References 142 publications

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

The Behavior of Matrix Metalloproteinases and Their Inhibitors in Colorectal Cancer

Clinical Relevance of Matrix Metalloproteases and their Inhibitors in Breast Cancer

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