Fig. 5: Functional cancer cell mitochondria are required for CAF reprogramming. | Nature Cancer

Fig. 5: Functional cancer cell mitochondria are required for CAF reprogramming.

From: MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation

Fig. 5

a, Basal respiration of HPFs subjected to MitoCeption with A431 or HaCaT mitochondria or mock treatment in comparison to A431 cells (n = 5 independent MitoCeptions per cell type). b, Proton leak in the same cultures as in a. c, Percentage of Ki67+ A431 cells and transwell migration of A431 cells cultured in CM of MitoCepted or mock-treated HPFs (n = 3 cultures per group). d, RT–qPCR for INHBA and IL6 using RNA from MitoCepted (mitochondria from MDA-MB-231 breast cancer cells) or mock-treated HPFs (n = 3 cultures per group). e, Clonogenicity of MDA-MB-231 cells cultured in CM from HPFs subjected to MitoCeption with MitoTracker green-stained mitochondria from MDA-MB-231 cells or mock treatment (n = 3 cultures per treatment group). f, Representative image of 3-week-old ear xenograft tumors (arrowheads) following intradermal coinjection of A431 cells and MitoCepted (with A431 mitochondria) or mock-treated HPFs and tumor volume at various time points (n = 5 tumors per group from different mice). g, Representative immunofluorescence stainings of tumors formed by A431 cells and MitoCepted or mock-treated HPFs for E-cadherin and FN1 (green) and MECA32 (red), counterstained with Hoechst (blue) (n = 5 tumors per group from different mice). h, Percentage of Ki67+ HPFs subjected to MitoCeption with A431 lmt mitochondria or mock treatment and RT–qPCR for INHBA using RNA from HPFs subjected to MitoCeption with A431 lmt mitochondria or mock treatment (n = 9 Ki67 or n = 3 RT–qPCR cultures per treatment group). i, Percentage of Ki67+ A431 cells (left) or transwell migration of A431 cells (right) cultured in CM from HPFs subjected to MitoCeption with A431 lmt mitochondria or mock treatment (n = 9 Ki67 or n = 3 transwell migration cultures per treatment group). j, Left, tumor volume at various time points during tumor development by A431 cancer cells coinjected with MitoCepted HPFs, which received mitochondria from control or lmt A431 cells (n = 4 tumors per group from different mice). Right, Histological stainings of a tumor from each group. Graphs show the mean ± s.e.m. An unpaired two-sided Student’s t-test (c–e,h,i) or two-sided one-way (a,b) or two-way (f,j) ANOVA with Bonferroni post hoc multiple comparison test was used to determine statistical significance. Scale bars, 200 μm (g) and 1 mm (j).

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