Fig. 4
Fibroblast functional characteristics are inherent to lineage or are acquired state-dependent. a Diagram of growth characteristics depicted as the cumulative population doublings (PDs) versus time (days) of iCAFs (yellow) and myCAFs (red) from their isolation in passage eight to passage 31 and 34, respectively. iCAFs grew on average 2.47 PDs ± 0.54 SD per passage and myCAFs grew on average 1.40 PDs ± 0.30 SD per passage (asterisk indicates p < 0.001, unpaired Student’s t-test). The significant growth advantage of iCAFs over myCAFs is reminiscent of the growth advantage of interlobular over lobular fibroblasts [4, 5]. b Line graph of quantified gel area expressed in percentage of initial gel in a contraction assay determined on day 2, 5, 7 and 8 for iCAFs (yellow), myCAFs (red), interlobular fibroblasts (blue) and lobular fibroblasts (green). * above myCAFs indicate significantly smaller gels versus any other group on the same day (p < 0.05). ¤ above iCAFs indicate significantly smaller gels versus interlobular- and lobular fibroblasts on the same day (p < 0.05). Statistical test used was one-way analysis of variance (ANOVA) with Benjamini–Hochberg multiple test correction. Error bars represent ± standard error of the mean (SEM). c Growth curve of mean tumor volume (mm3) in mice injected with MCF7 breast cancer cells without fibroblasts (black) or with iCAFs (yellow), myCAFs (red), interlobular fibroblasts (blue) or lobular fibroblasts (green). Tumors with lobular fibroblasts and myCAFs were significantly larger than with interlobular fibroblasts, iCAFs and without fibroblasts on days 43, 49, 58 and 64 (endpoint) as indicated by curly brackets and asterisks (*, p < 0.05 by one-way ANOVA with Benjamini–Hochberg multiple test correction). Error bars represent ± SEM