TNBC-secreted ZAG promotes fibrosis in the surrounding adipose tissue. A–D, The adipose tissue microenvironment of MDA-MB-468 xenografts depleted for ZAG is less fibrotic. A, Quantification and (B) representative image of Picro Sirius Red staining. C, Quantification and (D) representative image of αSMA staining. Sirius Red and αSMA staining was quantified in the region of interest defined as within 2 mm surrounding the tumor. E, The secretome of MDA-MB-468 cells promotes the expression of fibrotic genes Inhba, Tnc, Acta (αSma), and Ctgf in differentiating primary murine ASPCs (day 3 of adipogenic differentiation). TGFβ treatment of ASPCs for 3 days shows similar induced expression of fibrotic genes. A and C, Data are mean ± SEM. Data points are quantification of the staining of sections from 10 independent mice. P values calculated using Student t test. E, Data are mean ± SD. Data points show independent biological replicates from separate ASPC isolations. P values calculated using one-way ANOVA followed by Dunnett’s multiple comparison test. (ns, non-significant; *, P < 0.05; **, P < 0.01.)
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Verma et al. (2024) studied this question.
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