Nejvíce citovaný článek - PubMed ID 24012955
ERK and RSK regulate distinct steps of a cellular program that induces transition from multicellular epithelium to single cell phenotype
Arthrospira platensis, a blue-green alga, is a popular nutraceutical substance having potent antioxidant properties with potential anti-carcinogenic activities. The aim of our study was to assess the possible anti-angiogenic effects of A platensis in an experimental model of pancreatic cancer. The effects of an A platensis extract were investigated on human pancreatic cancer cells (PA-TU-8902) and immortalized endothelial-like cells (Ea.hy926). PA-TU-8902 pancreatic tumours xenografted to athymic mice were also examined. In vitro migration and invasiveness assays were performed on the tested cells. Multiple angiogenic factors and signalling pathways were analysed in the epithelial, endothelial and cancer cells, and tumour tissue. The A platensis extract exerted inhibitory effects on both migration and invasion of pancreatic cancer as well as endothelial-like cells. Tumours of mice treated with A platensis exhibited much lesser degrees of vascularization as measured by CD31 immunostaining (P = .004). Surprisingly, the VEGF-A mRNA and protein expressions were up-regulated in pancreatic cancer cells. A platensis inhibited ERK activation upstream of Raf and suppressed the expression of ERK-regulated proteins. Treatment of pancreatic cancer with A platensis was associated with suppressive effects on migration and invasiveness with various anti-angiogenic features, which might account for the anticancer effects of this blue-green alga.
- Klíčová slova
- Arthrospira platensis, angiogenesis, anticancer effects, carcinogenesis, pancreatic cancer,
- MeSH
- antioxidancia farmakologie MeSH
- antitumorózní látky farmakologie MeSH
- endoteliální buňky účinky léků MeSH
- inhibitory angiogeneze farmakologie MeSH
- lidé MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní farmakoterapie MeSH
- patologická angiogeneze farmakoterapie MeSH
- pohyb buněk účinky léků MeSH
- signální transdukce účinky léků MeSH
- Spirulina chemie MeSH
- upregulace účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- antitumorózní látky MeSH
- inhibitory angiogeneze MeSH
Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness.
- Klíčová slova
- AMT, EMT, invasion, plasticity, polarity,
- MeSH
- invazivní růst nádoru patologie MeSH
- lidé MeSH
- nádory patologie MeSH
- polarita buněk fyziologie MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH