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In vitro analysis reveals preferential detachment of INA-6 cells from homotypic aggregates over mesenchymal stem cells, highlighting mechanisms driving myeloma dissemination.
Time-lapse analysis of INA-6 detachment from INA-6 aggregates and hMSCs. A, Frequency of observed INA-6 aggregates that did or did not lose INA-6 cell(s). A total of 87 aggregates were evaluated per datapoint. B, Example of a “disseminating” INA-6 aggregate growing on fluorescently (PKH26) stained hMSC (from A–D). Dashed green lines are trajectories of detached INA-6 cells. Scale bar = 50 µm. C–E, Quantitative assessment of INA-6 detachments. A total of 45 detachment events were evaluated per datapoint. Seeding ratio INA-6:MSC = 4:1. C, Most INA-6 cells dissociated from another INA-6 cell and not from an hMSC [F(1, 3) = 298, P-unc = 4.2e-4]. D, Detachment frequency of aggregate size categories. E, Detachment frequency of INA-6 cells detaching as single, pairs or more than three cells. Statistics: (A): Paired t test; (C--E): Paired t test, two-factor RM-ANOVA; Datapoints represent three (A) or four (C–E) independent time-lapse recordings of cocultures with hMSCs from 2 (A) or 3 (C–E) unique donors.
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Kuric et al. (2024) studied this question.
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