Figure 2.

Multinucleated PGCCs are present in human HGSOC cell lines. (A) H&E-stained sections of xenografts of HGSOC cell lines OVCAR3 (p53-R248Q), TYK-NU (p53-R175H) and OVCA420 (p53-R273H) grown on the omentum of Foxn1^−/− immune compromised mice. The tumors exhibit distinct morphologies: OVCAR3, solid epithelial/mesenchymal-like; TYK-Nu, vascular-like; OVCA420, exclusively epithelial. The distribution of immune cells is also distinct for each tumor type: They are excluded from the solid OVCAR3 tumors, whereas in TYK-Nu and OVCA420 cells, scattered patches of immune cells are observed around the tumors and within the omental fat pad. t: tumor; i: immune cells; s: stromal cells. The inserts in (A) show multinucleated PGCCs. (B) Immunofluorescent images of sections of OVCAR3 xenografts showing large multinucleated PGCCs that express high levels of mutant p53 (green). Several cells also exhibit signs of stress as noted by the presence of γH2AX (red), a marker of DNA damage. (C) Immunofluorescent image of OVCAR3 cells in culture showing that cells are at different stages of the cell cycle. P53 (green) is nuclear in all cells that are not dividing, including PGCCs that are multinuclear (a) and (b). PGCC during abnormal cytokinesis (c). P53 is redistributed in cells undergoing normal mitosis where the condensed chromosomes are either at the midbody (d) or are undergoing cytokinesis (e). See Appendix for Supplemental Information describing the experimental procedures and histological/immunofluorescent imaging procedures for Figures 2–5).