Američtí lékaři před několika týdny představili objev, který pravděpodobně přispěje k léčbě rakoviny - zjistili, že pokud zablokují dvě látky, které podporují migraci nádorových buněk, mohou zabránit metastazování nádorů. Jenže čeští anatomové a přírodovědci mají na tento „objev" patent již od roku 2012. Bohužel český patent je pro světovou vědu a průmysl na okraji zájmu.
- MeSH
- fibroblasty MeSH
- interleukin-6 antagonisté a inhibitory MeSH
- interleukin-8 antagonisté a inhibitory MeSH
- lidé MeSH
- metastázy nádorů prevence a kontrola MeSH
- nádorové mikroprostředí * MeSH
- nádory farmakoterapie MeSH
- patenty jako téma * MeSH
- pohyb buněk účinky léků MeSH
- věda ekonomika MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
- Spojené státy americké MeSH
- MeSH
- antitumorózní látky * normy MeSH
- interleukin-6 antagonisté a inhibitory terapeutické užití MeSH
- interleukin-8 antagonisté a inhibitory terapeutické užití MeSH
- lidé MeSH
- metastázy nádorů prevence a kontrola MeSH
- objevování léků zákonodárství a právo MeSH
- patenty jako téma * MeSH
- Check Tag
- lidé MeSH
Tumour microenvironment plays a critical role in cell invasion and metastasis. To investigate the role of cancer-associated fibroblasts (CAFs) in melanoma cell invasiveness, we used 3D spheroid invasion assay. The effect of conditioned media from normal fibroblasts and CAFs cultivated alone or co-cultivated with melanoma cells on BLM or A2058 melanoma spheroid invasion was analysed. We found that conditioned media from CAFs and CAFs co-cultured with melanoma cells, especially, promote invasion and migration, without significant effect on melanoma cell proliferation. We further analysed the expression of pro-invasive cytokines IL-8 and IL-6 in media and found that melanoma cells are dominant producers of IL-8 and fibroblasts are dominant producers of IL-6 in 2D monocultures, while co-cultivation of CAFs with melanoma cells induces production/secretion of IL-6 and IL-8 into the media. The analyses of IL-6 levels in 3D cultures and human melanoma samples, however, revealed that at least in some cases IL-6 is also produced directly by melanoma cells. Analysis of the role of IL-6 and IL-8 in CAF-induced melanoma invasion, using neutralising antibodies, revealed that simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. In summary, these experiments indicate the important role of CAFs and IL-8 and IL-6 cytokines in melanoma cell invasiveness.
- MeSH
- ELISA MeSH
- fibroblasty asociované s nádorem účinky léků patologie MeSH
- imunohistochemie MeSH
- interleukin-6 analýza antagonisté a inhibitory metabolismus MeSH
- interleukin-8 analýza antagonisté a inhibitory metabolismus MeSH
- invazivní růst nádoru prevence a kontrola MeSH
- kokultivační techniky MeSH
- kultivační média speciální farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- melanom farmakoterapie metabolismus patologie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Oral administration of Lactobacillus spp. as probiotics is gaining importance in the treatment of intestinal inflammations. However, their mechanism of action is unknown. We investigated whether nonspecific binding Lactobacillus casei Shirota (LcS) and mannose-specific Lactobacillus plantarum 299v (Lp) and their spent culture supernatant (SCS) affect Salmonella enteritidis 857 (Se) growth, IL-8 and Hsp70 syntheses. In one set of experiments human enterocyte-like Caco-2 cells were infected with LcS, Lp or Se at 1-500 bacteria per cell for 1 h. In another set, cells were exposed to Se (0-200 per cell, 1 h) after exposure to lactobacilli (LB) (500 per cell, 30 min) or by co-incubation of Se and LB (1 h). The third set of experiments involved exposure of cells for 1 h to SCS or Se (100 per cell) pretreated (1 h) in SCS. The effect of LB SCS on Se growth was evaluated by agar plate diffusion test. IL-8 and Hsp70 were assessed over 2-24 h using ELISA and Western blotting, respectively. Neither LcS nor Lp affected the Se growth and IL-8 production. In addition, they did not induce Hsp70 expression by Caco-2 cells. Instead, their SCS inhibited the Se growth and IL-8 production and induced the expression of Hsp70 by both crypt- and villus-like cells. The beneficial effect of Lactobacillus spp. to the intestinal inflammations might be associated with a decrease in IL-8 levels. This effect could be mediated, at least in part, via a secreted antimicrobial product(s) either directly against the pathogens or indirectly through the synthesis of Hsp70.
- MeSH
- Caco-2 buňky MeSH
- ELISA MeSH
- imunologické faktory biosyntéza MeSH
- interleukin-8 antagonisté a inhibitory imunologie MeSH
- kokultivační techniky MeSH
- kultivační média chemie MeSH
- Lactobacillus casei metabolismus MeSH
- Lactobacillus plantarum metabolismus MeSH
- lidé MeSH
- probiotika MeSH
- proteiny tepelného šoku HSP70 biosyntéza MeSH
- Salmonella enteritidis patogenita růst a vývoj MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
