Fig. 1
Elevated COMP expression in the stroma of ovarian cancer tumors drives survival and metastasis. Tissue microarrays of ovarian cancer patients were immunohistochemically stained to evaluate the expression of COMP A in tumor cells and B stroma. C, D For data analysis, COMP intensity was scored and samples were grouped as weak (scores 0 and 1) or strong (scores 2 and 3) COMP expression. Scale bar: 100 µm. Kaplan–Meier analysis was applied to examine overall survival according to high and low COMP expression in C tumor cells and D stroma. In vivo, NXG mice were co-injected by either COMP-expressing CAFs (COMP) or mock-CAFs (Mock) together with SKOV3 cells, respectively. E Tumor volumes (mm3) were evaluated weekly and statistical significance was calculated with two way-ANOVA followed by Sidak’s post-test. F Tumor weight was measured at the end of the experiment, and the p-value was calculated by the Mann–Whitney test. G, H Immunohistochemistry analysis of pan-cytokeratin expression in lungs derived from mice co-injected with COMP-expressing CAFs and SKOV3 cells versus Mock CAFs combined with SKOV3 cells. The p-value was calculated by the Mann–Whitney test. Scale bar: 200 µm. I The effect of secreted COMP by CAFs on the migration ability of ovarian cancer cell lines, SKOV3 and OAW42 J, was evaluated by transwell migration co-culture assays. K, L The same assay was performed using COMP-expressing 3T3 cells and ID8 cells. The p-value was calculated using an unpaired t-test. Scale bar: 500 µm. M–O CAF cells were treated with TGF-β isoforms (10 ng/ml) and COMP transcriptional expression was evaluated by RT-qPCR. PBS and BSA-treated cells were also included as a control. HPRT1 was used as a reference gene, and the relative mRNA expression was calculated using the 2−ΔCt method. The p-value was calculated by the One-way ANOVA followed by Dunnett’s post-test. P < 0.05 was considered statistically significant. (*, **, ***, and ns indicate p < 0.05, p < 0.01, p < 0.001, and non-significant, respectively.) Data are representative of at least three independent experiments and graphs depict the mean with the standard deviation