Q112391807
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- MeSH
- biologické přípravky * dějiny farmakologie MeSH
- biotechnologie MeSH
- farmaceutická technologie MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- farmaceutická chemie trendy MeSH
- objevování léků MeSH
- výzkum organizace a řízení trendy MeSH
- Publikační typ
- rozhovory MeSH
Tumor markers known also as cancer or oncological markers are substances produced either by tumor or normal cells as a response to the presence of cancer . The markers are used for the detection, diagnosis, prognosis and control of treatment. There is no absolutely specific or universal cancer marker; therefore different markers for different cancer types are used in clinical practice. A problematic feature of cancer markers is their falsely positive results under physiological and non-cancer conditions.
In this study the levels of auto-antibodies formed against the activation peptide of procathepsin D were determined by the ELISA method using a synthetic multiantigen peptide containing the N-terminal amino acid sequence of the activation peptide of procathepsin D as a coating antigen. Based on the results auto-antibodies cannot be considered suitable cancer markers.
- MeSH
- akademie a ústavy organizace a řízení trendy využití MeSH
- biochemie metody organizace a řízení trendy MeSH
- farmaceutická chemie metody organizace a řízení trendy MeSH
- farmaceutická technologie trendy MeSH
- farmaceutický průmysl metody organizace a řízení trendy MeSH
- lidé MeSH
- výzkum trendy MeSH
- výzkumný projekt trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
- Geografické názvy
- Česká republika MeSH
For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans. In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling. Moreover, procathepsin D (pCD), secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy. Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell-pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above-mentioned processes. In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.
- MeSH
- Alzheimerova nemoc enzymologie MeSH
- apoptóza MeSH
- ateroskleróza enzymologie MeSH
- financování organizované MeSH
- inhibitory proteas terapeutické užití MeSH
- izoenzymy MeSH
- kathepsin D antagonisté a inhibitory genetika metabolismus MeSH
- lidé MeSH
- myši transgenní MeSH
- myši MeSH
- nádorové biomarkery metabolismus MeSH
- nádory enzymologie farmakoterapie MeSH
- prekurzory enzymů metabolismus MeSH
- protinádorové látky terapeutické užití MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
Human MDA-MB-231 derived breast cancer cell lines 1833 and 4175 have different metastatic potentials in terms of their tissue tropisms and aggressiveness. Cell line 1833 is specifically metastatic to the bone. The highly aggressive cell line 4175 is specific to the lung. We performed 2-DE analysis of the cell lines. We found 16 significantly changed protein spots, 14 protein spots were identified. Expression of cathepsin D, triosephosphate isomerase, phosphoglycerate kinase 1, heme binding protein 1 and annexin 2 could be correlated with the in vitro aggressiveness of the respective cell lines. Interstitial collagenase and dimethylargininase 2 were exclusive to the cell line 1833 and might contribute to its bone specificity. Serpin B9, cathepsin B chain b, galectin 3 and HSP 27 were changed in the lung specific cell line 4175. The possible contribution of identified proteins to differences in metastatic behavior of the cell lines is discussed.
- MeSH
- 2D gelová elektroforéza metody MeSH
- financování organizované MeSH
- hmotnostní spektrometrie metody MeSH
- invazivní růst nádoru MeSH
- kathepsin D biosyntéza MeSH
- kolagenasy biosyntéza MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové buněčné linie MeSH
- nádory prsu metabolismus patologie MeSH
- peptidy chemie MeSH
- počítačové zpracování obrazu MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Procathepsin D (pCD) is a major secreted protein in estrogen receptor-positive (ER+) breast cancer cell lines. Several independent studies have documented pronounced mitogenic effect of secreted pCD on cancer tissue-derived cell lines, including those from breast, lung, and prostate cancer. It has also been shown that the proliferative effect of pCD involves both autocrine and paracrine modes of action. Recent studies have suggested that pCD could act as a key paracrine communicator between cancer and stromal cells. We have shown earlier that the proliferative activity of pCD depends on the activation peptide sequence of pCD. The present study casts light on the mechanism by which pCD influences the proliferation of cancer cells expressing the ER. Results described in the current paper clearly show that pCD initiates secretion of cytokines interleukin-4 (IL-4), IL-8, IL-10, IL-13, macrophage inflammatory protein-1beta and (MIP-1beta) from such tumor cells. Secreted cytokines take part in the proliferation of the cancer cells, as proven by selective inhibition using antibodies. In addition, expression of cytokine receptors on tested cell lines corresponded to the effects of individual cytokines. An analogous pattern was also observed for fibroblasts, which, under physiologic conditions, are the cells in closest contact with the tumor tissue and play a role in tumor growth and invasion. Our observations were further supported by coculture experiments that are in agreement. Although very similar in response to addition of pCD, the invasive ER- cells do not secrete cytokines. Together with previous in vivo results, these data point to pCD as one of key molecules for therapeutic attack in breast cancer.
- MeSH
- autokrinní signalizace MeSH
- cytokiny sekrece MeSH
- financování organizované MeSH
- kathepsin D sekrece terapeutické užití MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie patologie sekrece MeSH
- parakrinní signalizace MeSH
- prekurzory enzymů sekrece terapeutické užití MeSH
- proliferace buněk MeSH
- receptory pro estrogeny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
