MECHANICAL HETEROGENIZATION OF LEWIS LUNG CARCINOMA CELLS CAN IMPROVE ANTIMETASTATIC EFFECT OF DENDRITIC CELLS

2012 ◽  
Vol 12 (03) ◽  
pp. 1250037
Author(s):  
NATALYA KHRANOVSKAYA ◽  
VALERII OREL ◽  
YURIY GRINEVICH ◽  
OXANA ALEKSEENKO ◽  
ANDRIY ROMANOV ◽  
...  

The effect of mechanically heterogenized (MCH) microparticles of tumor cells (TCs) on antimetastatic action of dendritic cells (DCs) is studied in C57BL/6 mice with Lewis' carcinoma. DCs isolated from mice spleens and loaded with MCH-TCs are analyzed with flow cytometry methods. MCH-TCs are analyzed with optical and/or electron microscopy. The paper describes an original high-precision medical microvibromill with high-acceleration linear induction motor that generates magnetic levitation to produce mechanical heterogenization of TCs. MCH-TCs have a more asymmetric morphology, larger surface and higher internal structure heterogeneity, and higher concentration of free radicals with respect to conventionally treated TCs. The rate of DCs maturity, being affected by pre-incubation with MCH-TCs is found to be higher than its counterpart treated with conventional TCs. DCs loaded with MCH-TCs show a significantly higher ability to induce proliferation of allogeneic lymphocytes in mixed leukocyte reaction. The inhibition index of metastases formation increases from 42% (conventional TCs) to 66% when DCs are treated with MCH-TCs. The present results demonstrate the feasibility of increasing antimetastatic activity of DCs-based vaccines when MCH-TCs is used for their loading. Mathematical model is developed in order to simulate the processes of capture, processing and presentation of tumor antigens by DCs when using conventional TCs or MCH-TCs.

2009 ◽  
Vol 182 (5) ◽  
pp. 2795-2807 ◽  
Author(s):  
Ingrid E. Dumitriu ◽  
Donald R. Dunbar ◽  
Sarah E. Howie ◽  
Tariq Sethi ◽  
Christopher D. Gregory

2015 ◽  
Vol 117 (17) ◽  
pp. 17D123 ◽  
Author(s):  
J. Devkota ◽  
M. Howell ◽  
P. Mukherjee ◽  
H. Srikanth ◽  
S. Mohapatra ◽  
...  

Life Sciences ◽  
2003 ◽  
Vol 72 (15) ◽  
pp. 1705-1716 ◽  
Author(s):  
Sheng-Teng Huang ◽  
Rong-Chi Yang ◽  
Li-Jiun Yang ◽  
Pei-Nir Lee ◽  
Jong-Hwei S. Pang

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Kunpei Fukasawa ◽  
Kako Hanada ◽  
Kei Ichikawa ◽  
Masanori Hirashima ◽  
Takahiro Takagi ◽  
...  

Abstract Background Transforming growth factor (TGF)-β is a multifunctional cytokine involved in cell differentiation, cell proliferation, and tissue homeostasis. Although TGF-β signaling is essential for maintaining blood vessel functions, little is known about the role of TGF-β in lymphatic homeostasis. Methods To delineate the role of TGF-β signaling in lymphatic vessels, TβRIIfl/fl mice were crossed with Prox1-CreERT2 mice to generate TβRIIfl/fl; Prox1-CreERT2 mice. The TβRII gene in the lymphatic endothelial cells (LECs) of the conditional knockout TβRIIiΔLEC mice was selectively deleted using tamoxifen. The effects of TβRII gene deletion on embryonic lymphangiogenesis, postnatal lymphatic structure and drainage function, tumor lymphangiogenesis, and lymphatic tumor metastasis were investigated. Results Deficiency of LEC-specific TGF-β signaling in embryos, where lymphangiogenesis is active, caused dorsal edema with dilated lymphatic vessels at E13.5. Postnatal mice in which lymphatic vessels had already been formed displayed dilation and increased bifurcator of lymphatic vessels after tamoxifen administration. Similar dilation was also observed in tumor lymphatic vessels. The drainage of FITC-dextran, which was subcutaneously injected into the soles of the feet of the mice, was reduced in TβRIIiΔLEC mice. Furthermore, Lewis lung carcinoma cells constitutively expressing GFP (LLC-GFP) transplanted into the footpads of the mice showed reduced patellar lymph node metastasis. Conclusion These data suggest that TGF-β signaling in LECs maintains the structure of lymphatic vessels and lymphatic homeostasis, in addition to promoting tumor lymphatic metastasis. Therefore, suppression of TGF-β signaling in LECs might be effective in inhibiting cancer metastasis.


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