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• W1898032945 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20065571 A profilin-like protein, PA19, common to many protozoa, was recently found to be a ligand for toll-like receptor TLR12 [Science,308,1626–1629 (2005)]. It is able to activate dendritic cells (DCs) in vitro and, when injected intraperitoneally (I.P.) in mice, to drastically reduce tumor formation by murine sarcoma S-180 [Int. J. Cancer, 114, 756–765 (2005)]. We have found that when PA19 is expressed as a transgene in human HT1080 fibrosarcoma cells, tumor formation in athymic mice is reduced [Proc. Amer. Assoc. Cancer. Res., 46, 3365 (2005)]. A report by Janke et al., (2000) showed that expression of the profilin 1 (PFN1) gene as a transgene in the human breast cancer cell line, CAL51, reduced the tumor-forming ability of these cells. This effect is believed to be the result of PFN1's interference in microfilament organization via its actin binding site [Mol. Biol. Cell, 15, 1600–1608 (2004)]. To determine whether the tumor suppressor activity of PA19 involves a mechanism similar to PFN1, we compared tumor formation by HT1080 cell lines, expressing PA19 either in an intracellular form (nPA19), or in a secreted form (sPA19). Eight cell lines stably-expressing nPA19, six expressing sPA19, five expressing an empty vector, and the parent cell line were compared. All were found to have similar growth characteristics in vitro . The expression of PA19 in the cell lines was quantified by determining the ability of the cell lysates, or conditioned media to activate DCs in in vitro assay. Mice were injected subcutaneously with 1 × 106 cells in the right or left rear flank. Blood analysis of mice injected with cell lines expressing sPA19 showed its presence as well as elevated levels of IL-12. All sites injected with parent line, or empty vector cell lines began developing tumor within 10 days after injection. On average, sites injected with cell lines expressing either form of PA19 were tumor-free for a longer period and the tumors grew more slowly than at the sites injected with the vector controls. All mice injected with cells carrying the empty vector were dead at 150 days and 40% expressing sPA19 remained tumor free for >150 days. Complete remission was observed in three mice (one injected with a cell line expressing nPA19, and two expressing sPA19). The sPA19 cell lines were less tumorigenic than the nPA19 cell lines as judged by tumor size (p=0.012) and the rate of tumor growth (p=0.027). These results support the hypothesis that the mechanisms of tumor suppression by PA19 and PFN1 are different. None of the surviving mice injected with the cell lines expressing sPA19 showed sign of immunity towards the secondary I.P. injection of the parent HT1080 cells indicating that there is no long-lasting protection involved in the observed tumor suppression mechanism. (Supported by NIH CA98305 to JJM)." @default.
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• W1898032945 date "2006-04-15" @default.
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• W1898032945 title "Tumorigenicity of human fibrosarcoma HT1080 cells expressing protein PA19 in either secreted or non-secreted form, as evaluated in athymic mice." @default.
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