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. 2020 Jul 27;12(8):2063. doi: 10.3390/cancers12082063

Figure 6.

Figure 6

Downstream Activation of Hedgehog through PDGF-BB/PDGFR-β Signaling in Ovarian CSC and MSC Crosstalk. (A) Gene expression analysis of Hedgehog pathway elements in OVCAR3 CSC mono-cultures (black line), OVCAR3 CSC/MSC or OVCAR3 CSC/siPDGFB MSC heterospheroids. Gene qPCR data demonstrates a significant loss in Hedgehog ligands (SHH and IHH; **** p < 0.0001, two-way ANOVA, n ≥ 3) upon PDGFB knockdown. Additionally, signaling elements within the Hedgehog pathway are also significantly downregulated (* p < 0.05, two-way ANOVA) upon PDGF knockdown including Smoothened (SMOO) and GLI1, indicating that PDGFB might be upstream of Hedgehog ligand secretion and/or signaling (n ≥ 3). (B) OVCAR3 CSC/MSC and OVCAR3 CSC/siPDGFB MSC heterospheroids were treated with 1 mM sonidegib, a Smoothened inhibitor, and carboplatin to determine the change in IC50. Hedgehog inhibition compounded with knockdown of PDGFB, resulting in a lower carboplatin IC50 in CSC/MSC heterospheroids (n ≥ 3). (C) Representative phase contrast microscopy images of the heterospheroids when treated with 1 mM sonidegib and 100 µM carboplatin, indicating significant visual cell death and loss of spheroid integrity.