Role of tumor/endothelial cell interactions in tumor growth and metastasis.

BACKGROUND: It is known that interactions between tumor and endothelial cells have a significant influence on the growth and metastasis of malignant tumors. AIM: To study the reciprocal effect of Lewis lung carcinoma (LLC) and endothelial cells on the growth rate of each other upon their co-cultivation in vitro and to assess the contribution of such tumor/endothelial cell crosstalk to in vivo LLC growth and metastasis. MATERIALS AND METHODS: Two variants of Lewis lung carcinoma cells, high-metastatic (LLC) and low-metastatic (LLC/R9), and murine aorta endothelial cell line (MAEC) were used. Kinetics of tumor cell growth in vitro and in vivo, electrokinetic properties of tumor cells and their adhesion to endothelial monolayer, and the number of tumor and endothelial viable cells after 1-day contact or non-contact co-cultivation were estimated. RESULTS: LLC/R9 had significantly higher growth rate in vivo (as opposed to in vitro) than LLC. However, the number and volume of lung metastatic lesions in LLC/R9-bearing mice were 4.5-fold (p < 0.05) and 3.6-fold lower (p < 0.05), respectively, compared to those in LLC-bearing mice. Non-contact co-cultivation of LLC/R9 + MAEC caused more than a 34% (p < 0.05) LLC/R9-induced increase in the number of MAEC and a 60% (p < 0.05) MAEC-induced increase in the number of LLC/R9 cells as compared to those of corresponding controls (cells cultured alone). In contrast, in the case of LLC + MAEC, both the number of LLC and MAEC cells after their non-contact co-cultivation and cultivation alone did not differ significantly. Contact co-cultivation LLC+MAEC (in contrast to LLC/R9+MAEC) caused more than a 50% (p < 0.01) LLC-induced decrease in the number of MAEC and a 50% decrease (p < 0.05) MAEC-induced in the number of LLC cells as compared to the corresponding controls. Both tumor cell variants showed a bimodal distribution of cells by ζ-potential, but in the case of LLC there was observed a shift towards high values due to 52% of cells with a surface charge density > 10 C/m2, while in the case of LLC/R9 such a subpopulation was absent and 19% of cells had a surface charge < 5 C/m2. The number of LLC cells that adhered to the monolayer of endothelial cells was by 65% (p < 0.05) higher than that of LLC/R9 cells. CONCLUSION: Obtained data demonstrated that the tumor/endothelial cell relationships might reflect the features of tumor growth and metastasis of a malignant tumor.

Application of gold and silver nanoparticles for selective assay of spermine in mixture with spermidine.

AIM: To assess the applicability of the novel technique based on the detection of spermine in solutions by spectrocolorimetric method using gold and silver colloidal nanoparticles. MATERIALS AND METHODS: Colloidal solution of gold nanoparticles were synthesized by chemical reduction of tetrachlorauric acid with trisodium citrate. Colloidal solution of silver nanoparticles was obtained by chemical reduction of silver nitrate with tryptophan. The absorption spectra of gold/silver metal colloids and their mixtures with polyamines were recorded. RESULTS: The increase of spermine concentration in solution caused the change in the intensity of the band of localized surface plasmon resonance that was not affected by the excess of spermidine. The color shift in colloidal gold due to its aggregation with spermine was registered spectrophotometrically. CONCLUSION: The principal possibility of selective quantification of spermine in the presence of spermidine in extremely high concentration using colloidal gold has been shown. This method can be used to assay selectively spermine in biological fluids.

Influence of aconitine-containing herbal extract BC1 on proliferative and electrokinetic characteristics of endothelial cells.

AIM: To evaluate the influence of new antitumor preparation BC1 produced on the base of Aconitum species on viability and electrokinetic properties of endothelial cells for estimation of mechanisms of its antitumor and antimetastatic activity. MATERIALS AND METHODS: Cytotoxic/cytostatic action of BC1 toward murine aorta endothelial cells (MAEC) and tumor LLC/R9 cells was studied using MTT-test. Apoptotic rate of MAEC was performed by flow cytometry. Electrokinetic properties of MAEC were determined by linear rate of their migration in electric field with the voltage of 20 V/cm. RESULTS: After 24 h of incubation with BC1, IC50 for actively proliferating was 0.95 -/+ 0.06 microg/ml and was 9-fold and 14-fold lower (p < 0.05) than that index for confluent endotheliocytes and LLC/R9 cells respectively. The ability of BC1 to alter electrokinetic characteristics of MAEC and to induce apoptosis has been demonstrated. At the concentration of IC50/10, 1 caused 2-fold decrease of zeta-potential and surface density of charge of compared to the control (p < 0.05) whilst at the concentration of IC50/20 - inversion of surface charge of the majority (80%) of the cells in association with BC1-induced apoptosis. CONCLUSION: High sensitivity of actively proliferating MAEC to the action of BC1 was revealed as well as the ability of that preparation to cause apoptosis and inversion of surface charge of endothelial cells.