The cathepsin family and their role in colorectal cancer

Kuester, Doerthe; Lippert, H.; Roessner, Albert; Krueger, Sabine

doi:10.1016/j.prp.2008.04.010

Cited by 104 publications

(88 citation statements)

References 67 publications

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“…Based on the balance between its proteolytic and inhibitory activity in tissue and our results that serpinA3 expression in cancer tissue is lower than that in paired normal tissues it may be suggested that a high activity of proteinases is linked to tumour growth and aggressiveness. Proteinases play a role in cancer metastasis (1)(2)(3)(4)(5). Notably, the down-regulated serpinA3 expression in cancer tissue noted in the present study appears to depend on regulatory factors secreted from tumour cells.…”

Section: Discussionmentioning

confidence: 49%

“…It has been widely reported that proteinases that are expressed in cancerous tissue promote invasiveness and tumour progression (1)(2)(3)(4)(5). Recently, it has been reported that cathepsin G activates pro-MMP-9 (16) and that negative MMP-9 expression is associated with a longer survival time in CRC patients (17).…”

Section: Discussionmentioning

confidence: 99%

“…Matrix metalloproteinase (MMP) expression has been linked to tumour aggressiveness and tumour invasion in a wide range of cancers, such as colorectal cancer (CRC) (2)(3)(4). Cathepsins, another class of proteases, also play a role in invasion and metastasis of CRC (5). Serine protease inhibitors (serpins) belong to a protein superfamily with inhibitory activity against proteases.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas

et al. 2011

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Abstract. Proteases facilitate a number of steps in cancer progression. The serine protease inhibitors (serpins) are a protein superfamily with inhibitory activity against proteases. One of these proteases, serpinA3, appears to have a multifaceted role and is associated with inflammatory reactions, Alzheimer's disease, malignant melanoma and gastric cancer. To gain insight into the potential effect of serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we noted a significantly lower serpinA3 level in cancer tissue compared to paired normal tissue. Moreover, the tumour serpinA3 level tended to be higher in disseminated disease as compared to localised disease. No significant difference in the plasma levels of serpinA3 was noted in the patients when compared to the controls. However, plasma serpinA3 and C-reactive protein (marker of inflammation) in the CRC patients and controls were significantly positively correlated. To confirm and detect localization of serpinA3 expression, immunohistochemistry was performed. Immunohistochemistry showed heterogeneous immunoreactivity in epithelial cells in the cancer and normal tissue and extracellular staining within bands of stroma as well as in some stromal cells. A Taq Man system was used to investigate a single nucleotide polymorphism (rs4934) in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion and expression. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions, nor were associations noted between clinical characteristics and serpinA3 levels. In conclusion, an altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC progression. SerpinA3 concentrations in plasma appear to be correlated with systemic inflammation, but do not appear to be specific to CRC patients. Further studies are warranted to improve our understanding of the role of serpinA3 in CRC.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas

et al. 2011

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“…Lysosomal proteases (cathepsins) are apparently the most important group of these enzymes. Lysosomal cathepsins can be categorized as cysteine (cathepsins B, C, F, H, K, L, O, S, V, W and X), aspartic (cathepsins D and E) and serine (cathepsin G) proteases (Eskelinen and Saftig, 2008, Kuester et al, 2008, Turk et al, 2002. They have a pH optimum of around 5, although several of them remain active even at neutral pH from minutes (cathepsin L) to hours (cathepsin S) (Droga-Mazovec et al, 2008).…”

Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

172

134

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Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

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“…Cathepsins are a class of lysosomal peptidases which (Kuester et al, 2008;Szajda et al, 2008;Yu et al, 2005). These observation clearly indicated that these cathepsins might be involved in CRC development and growth.…”

Section: Proteolytic Enzymesmentioning

confidence: 99%

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

Zhang

Chen²,

Ding³

2012

Asian Pacific Journal of Cancer Prevention

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Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra-and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

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The cathepsin family and their role in colorectal cancer

Cited by 104 publications

References 67 publications

Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas

Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas

The role of lysosomes in iron metabolism and recycling

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

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