Low dose chemotherapeutic drugs without overt cytotoxic effects decrease the secretion of VEGF by cultured human tumor cells: A tentative relationship between drug type and tumor cell type response

Species-specific lncRNAs significantly determine species-specific functions through various ways, such as epigenetic regulation. However, there has been no study focusing on the role of species-specific lncRNAs in other species yet. Here, we found that siRNAs targeting mouse-specific lncRNA AA388235 could significantly induce death of human tumor cells, although it has no effect on mouse tumor cells and normal human cells. The mechanism studies showed that these siRNAs could activate the response of human tumor cells to exogenous nucleic acids, induce pyroptosis and apoptosis in the presence of GSDME, but induce apoptosis in the absence of GSDME. They also significantly inhibited the growth of human tumor cells in vivo. 17 siRNAs were designed for seven more mouse-specific lncRNAs selected randomly, among which 12 siRNAs targeting five lncRNAs induced death in human tumor cell. Our study not only demonstrates that the siRNAs designed for knocking down mouse-specific lncRNA AA388235 can be potential tumor therapeutic drugs, but also suggests that non-human species-specific lncRNAs are a huge potential library that can be used to design siRNAs for tumor treatment. Large-scale screening based on this is promising.

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Systematic analysis of the human tumor cell binding to human vs. murine E- and P-selectin under static vs. dynamic conditions

Glycobiology ◽

10.1093/glycob/cwaa019 ◽

2020 ◽

Vol 30 (9) ◽

pp. 695-709 ◽

Cited By ~ 1

Author(s):

Sarah Starzonek ◽

Hanna Maar ◽

Vera Labitzky ◽

Daniel Wicklein ◽

Charlotte Rossdam ◽

...

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Human Tumor ◽

Sialyl Lewis X ◽

Metastasis Formation ◽

Human Tumor Cells ◽

Systematic Analysis ◽

Dynamic Conditions ◽

Immunodeficient Mice ◽

Static Conditions

Abstract Endothelial E- and P-selectins promote metastasis formation by interacting with sialyl-Lewis X and A (sLeX/sLeA) on circulating tumor cells. This interaction precedes extravasation and can take place under dynamic and static conditions. Metastasis formation is often studied in xenograft models. However, it is unclear whether species differences exist in the ligand specificity of human (h) vs. murine (m) selectins and whether different ligands are functional under dynamic vs. static conditions. We systematically compared the h vs. m E- and P-selectin (ESel/PSel) binding of a range of human tumor cells under dynamic vs. static conditions. The tumor cells were categorized by their sLeA/X status (sLeA+/sLeX+, sLeA−/sLeX+ and sLeA−/sLeX−). The general biological nature of the tumor–selectin interaction was analyzed by applying several tumor cell treatments (anti-sLeA/X blockade, neuraminidase, pronase and inhibition of O/N-glycosylation). We observed remarkable differences in the static vs. dynamic interaction of tumor cells with h vs. m ESel/PSel depending on their sLeA/X status. The tumor cell treatments mostly affected either static or dynamic as well as either h- or m-selectin interaction. mESel showed a higher diversity of potential ligands than hESel. Inhibition of O-GalNAc-glycosylation also affected glycosphingolipid synthesis. Summarized, different ligands on human tumor cells are functional under static vs. dynamic conditions and for the interaction with human vs. murine ESel/PSel. Non-canonical selectin ligands lacking the sLeA/X glycan epitopes exist on human tumor cells. These findings have important implications for the current development of glycomimetic, antimetastatic drugs and encourage the development of immunodeficient mice with humanized selectins.

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Ultrastructure of double minutes from a human tumor cell line.

The Journal of Cell Biology ◽

10.1083/jcb.83.3.663 ◽

1979 ◽

Vol 83 (3) ◽

pp. 663-666 ◽

Cited By ~ 22

Author(s):

P E Barker ◽

E Stubblefield

Keyword(s):

Electron Microscopy ◽

Chemical Analysis ◽

Tumor Cell ◽

Cell Line ◽

Tumor Cells ◽

Human Tumor ◽

Tumor Cell Line ◽

Human Tumor Cells ◽

Human Tumor Cell ◽

Double Minutes

Double minutes (dm) have been isolated from human tumor cells by zonal centrifugation and by differential pelleting of chromosome suspsension. These methods allowed collection of dm in sufficient quantity and purity for visualization with electron microscopy. Ultrastructurally, the chromatin fibers in dm resemble thrance fragments was found. When the two isolation protocols were compared, differential pelleting was shown to increase purity twofold to 85% dm by mass. The differential pelleting procedure enables easy collection of dm in sufficient quantity and purity for chemical analysis.

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