Inhibitor E

The cells were injected into mice as described in the next section.A portion of the cells that were used in the injections was seeded back into a culture plate to determine plating ef ficiency.Theviability was higher than, and the plating ef ficiency was greater than. The treatments were admin istered tw ice a week until the experiment was terminated.To mon itor tumor grow th during the treatment, we estimated tumor size by measuring biweekly the longest and shortest diameters of the tumor and by averaging the two measurements.At the end of the experiment, the mice were anesthetized and per fused through the heartwith PBS, and the tumors and the lungs were excised and weighed.The lungs also were examined for the number of metastatic foci.The tissues were fixed in paraformaldehyde for hand stored in ethanol.In prev ious work, we found that systemic treatmentwith sFN, a polymer of fibronectin that is prepared by mix ing fibronectin and anastellin, had a strong Ibuprofen antimetastatic ef fect when used to treat mice bearing large tumors.This ef fect was achieved even though sFN had little or no ef fect on the grow th of the primarytumors. In the present study, we started the treatments at an earlier stage of tumor development and found that sFN sign ificantly inhibited the grow th of C human melanoma xenografttumors. Indeed, we found that adding anastellin to a fibrinogen solution in vitro caused turbidity, producing a polymeric compound, sFBG. However, a higher concentration of fibrinogen than fibronectin was needed to produce the same degree of polymerizationwith anastellin.In subsequent tumor treatment experiments, we compared sFN and sFBG at the same approx imate levels of polymerization.Comparing the antitumor activities of the various anastellin compounds, we found that sFBG inhibited tumor FX1 growth approx imately as effectively as anastellin alone or sFN.Similar results were obtained with three different tumors, C. In some experiments, a peptide analogous to anastellin but derived from the th type III repeat of fibronectin and had no effect on the growth of the breast carcinoma tumors. A ll of the vehicletreated micewith C tumors and most of the micewith KR IB tumors developed macroscopic lung metastases; the MDAMB tumors did not metastasizewithin the time frame of our experiments.In agreementwith earlier results, only a few micewith C or KR IB tumors developed metastatic foci in the lungs when treatedwith sFN. SFBG was studied less extensively but seemed to have an ef fect on metastasis similar to that of sFN and anastellin.Anastellin is a fibronectin fragment that binds to and polymerizes fibronectin and fibrinogen.Anastellin also inhibits metastasis.We prev iously have shown that sFN, a fibronectin polymer induced by anastellin, has a potent antimetastatic activ ity in experimental and spontaneous metastasis models. In that study, systemic treatment of the tumorbearing micewith sFN or anastellin had no sign ificant ef fect on tumor grow th.In contrast, we found in the present study that tumor grow th was inhibited by these compounds, as well as by sFBG, a fibrinogen polymer generated by treating soluble fibrinogenwith anastellin.

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