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Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity

Figure 5

Distinct “go” and “grow” features of two cell subpopulations in U251 with optimal equilibrium benefiting overall tumor growth.

A, H&E images (2X) and FISH images (100X) of i.c. xenografts derived from NS1. Arrowhead, double and single arrow point to cells with 1, 2, and 3 copies of Chr7, respectively. B, comparison of cell population equilibrium in NS1 (in vitro culture) and the derived i.c. tumors. C, fluorescence images of i.c. xenografts derived from co-implantation of RFP-labeled STIC-enriched U251-NS and GFP-labeled U251 in a 9∶1 ratio. D–E, immunofluorescence images of i.c. xenografts from co-implantation of the two lines in a 1∶99 ratio, with purple color marking BMI1 and MELK expression by RFP cells at the tumor boundary and their expression of CD133 and SPARC in vascular mimicry within the bulk tumor mass. F, confocal immunofluorescence images of i.c. xenografts derived from 100% RFP cells, with yellow color marking co-localization of RFP with CD31 or GFAP. G, Kaplan-Meier survival curves of mice after implanting a mixture of U251 parental and STIC-enriched NS subculture. Adjusted Hazard ratios (HRs) from the stratified analysis and p-value are from Cox regression analyses examining the effect of STIC percentage on survival.

Figure 5

doi: https://doi.org/10.1371/journal.pone.0080898.g005