Nejvíce citovaný článek - PubMed ID 6090232
Syngeneic lines of chickens. VII. The lines derived from the recombinants at the B complex (MHC) of Rous sarcoma regressor and progressor inbred lines of chickens
Systems of antigen delivery into antigen-presenting cells represent an important novel strategy in chicken vaccine development. In this study, we verified the ability of Rous sarcoma virus (RSV) antigens fused with streptavidin to be targeted by specific biotinylated monoclonal antibody (anti-CD205) into dendritic cells and induce virus-specific protective immunity. The method was tested in four congenic lines of chickens that are either resistant or susceptible to the progressive growth of RSV-induced tumors. Our analyses confirmed that the biot-anti-CD205-SA-FITC complex was internalized by chicken splenocytes. In the cytokine expression profile, several significant differences were evident between RSV-challenged progressor and regressor chicken lines. A significant up-regulation of IL-2, IL-12, IL-15, and IL-18 expression was detected in immunized chickens of both regressor and progressor groups. Of these cytokines, IL-2 and IL-12 were most up-regulated 14 days post-challenge (dpc), while IL-15 and IL-18 were most up-regulated at 28 dpc. On the contrary, IL-10 expression was significantly down-regulated in all immunized groups of progressor chickens at 14 dpc. We detected significant up-regulation of IL-17 in the group of immunized progressors. LITAF down-regulation with iNOS up-regulation was especially observed in the progressor group of immunized chickens that developed large tumors. Based on the increased expression of cytokines specific for activated dendritic cells, we conclude that our system is able to induce partial stimulation of specific cell types involved in cell-mediated immunity.
- MeSH
- antigeny virové imunologie MeSH
- buněčná imunita imunologie MeSH
- CD antigeny imunologie MeSH
- cytokiny fyziologie MeSH
- dendritické buňky imunologie virologie MeSH
- kur domácí imunologie virologie MeSH
- lektiny typu C imunologie MeSH
- protilátky bispecifické imunologie MeSH
- ptačí sarkom imunologie prevence a kontrola MeSH
- receptory buněčného povrchu imunologie MeSH
- vedlejší histokompatibilní antigeny imunologie MeSH
- virové vakcíny imunologie MeSH
- virus Rousova sarkomu imunologie MeSH
- zvířata kongenní imunologie virologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny virové MeSH
- CD antigeny MeSH
- cytokiny MeSH
- DEC-205 receptor MeSH Prohlížeč
- lektiny typu C MeSH
- protilátky bispecifické MeSH
- receptory buněčného povrchu MeSH
- vedlejší histokompatibilní antigeny MeSH
- virové vakcíny MeSH
BACKGROUND: Although there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process. RESULTS: We analyzed the dependence of amoeboid invasiveness of rat and chicken sarcoma cells and the metastatic activity of chicken cells on individual elements of the Rho/ROCK/MLC pathway. In both animal models, inhibition of Rho, ROCK or MLC resulted in greatly decreased cell invasiveness in vitro, while inhibition of extracellular proteases using a broad spectrum inhibitor did not have a significant effect. The inhibition of both Rho activity and MLC phosphorylation by dominant negative mutants led to a decreased capability of chicken sarcoma cells to metastasize. Moreover, the overexpression of RhoA in non-metastatic chicken cells resulted in the rescue of both invasiveness and metastatic capability. Rho and ROCK, unlike MLC, appeared to be directly involved in the maintenance of the amoeboid phenotype, as their inhibition resulted in the amoeboid-mesenchymal transition in analyzed cell lines. CONCLUSION: Taken together, these results suggest that protease-independent invasion controlled by elements of the Rho/ROCK/MLC pathway can be frequently exploited by metastatic sarcoma cells.
- MeSH
- invazivní růst nádoru MeSH
- kinázy asociované s Rho metabolismus MeSH
- krysa rodu Rattus MeSH
- kur domácí MeSH
- lehké řetězce myosinu metabolismus MeSH
- nádorové buněčné linie MeSH
- pohyb buněk MeSH
- Rho proteiny vázající GTP metabolismus MeSH
- sarkom metabolismus patologie MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kinázy asociované s Rho MeSH
- lehké řetězce myosinu MeSH
- Rho proteiny vázající GTP MeSH
Metastatic spreading of cancer cells is a highly complex process directed primarily by the interplay between tumor microenvironment, cell surface receptors, and actin cytoskeleton dynamics. To advance our understanding of metastatic cancer dissemination, we have developed a model system that is based on two v-src transformed chicken sarcoma cell lines-the highly metastatic parental PR9692 and a non-metastasizing but fully tumorigenic clonal derivative PR9692-E9. Oligonucleotide microarray analysis of both cell lines revealed that the gene encoding the transcription factor EGR1 was downregulated in the non-metastatic PR9692-E9 cells. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from parental PR9692 cells. Microarray analysis of EGR1 reconstituted cells revealed the activation of genes that are crucial for actin cytoskeleton contractility (MYL9), filopodia formation (MYO10), the production of specific extracellular matrix components (HAS2, COL6A1-3) and other essential pro-metastatic abilities.
- MeSH
- buněčná adheze MeSH
- buněčné linie MeSH
- cytoskelet metabolismus MeSH
- fenotyp MeSH
- kinetika MeSH
- kur domácí MeSH
- metastázy nádorů genetika MeSH
- nádorová transformace buněk genetika patologie MeSH
- onkogenní protein pp60(v-src) genetika metabolismus MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- protein 1 časné růstové odpovědi genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- sarkom genetika patologie MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- onkogenní protein pp60(v-src) MeSH
- protein 1 časné růstové odpovědi MeSH
We report that the cloned DNA harboring the long terminal repeat (LTR), v-src, LTR proviral structure is tumorigenic in chickens of the Prague congenic lines. The growth rate of these tumors is by far the highest in the recombinant CC.R1 line, the B haplotype of which is composed of the B-F/L4 and B-G12 subregions originating from different naturally occurring haplotypes. Some of the tumors induced by the LTR, v-src, LTR DNA are repeatedly transplantable in syngeneic chickens, maintain unaltered provirus, and express v-src mRNA. Differences in the response to challenge with Rous sarcoma virus (RSV) and LTR, v-src, LTR DNA on a given experimental model are compared and possible involvement of an interaction between B-F/L and B-G region genes is considered. Regression of the LTR, v-src, LTR DNA-induced tumors did not prevent the formation and growth of tumors induced subsequently by RSV.
- MeSH
- buněčné dělení genetika MeSH
- DNA nádorová fyziologie MeSH
- geny src fyziologie MeSH
- klonování DNA MeSH
- kur domácí MeSH
- nádory genetika mikrobiologie MeSH
- northern blotting MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- proviry MeSH
- repetitivní sekvence nukleových kyselin fyziologie MeSH
- Southernův blotting MeSH
- testy genetické komplementace MeSH
- viry ptačího sarkomu MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA nádorová MeSH
