Stromal factors involved in human prostate cancer development, progression and castration resistance

To detect new predictive markers from the prostate cancer tissue, to study the expression by cultured cancer-associated fibroblasts (CAFs) of stromal factors implicated in prostate carcinogenesis, and to compare their expressions in localized, metastatic, castration-sensitive (CSCP), castration-resistant prostate tumors (CRCP) as well as in fibroblasts from benign prostatic hyperplasia (BPH). The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGF beta, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NF kappa B), stroma/epithelium interaction (CDH11, FAP, CXCL12 and CXCL14) and chaperones (HPA1A and HSF1), was evaluated in cultured fibroblasts both from BHP and prostate carcinomas (PCa). After isolation and culture of fibroblasts by biopsy specimens, RNA was isolated and genomic studies performed. Finally, 5 BPH and 37 PCa specimens were selected: clinically localized (19), metastatic (5), CSCP (7) and CRPC (6). Interleukin-17 receptor (IL-17RB) was highly expressed in CAFs compared with fibroblasts from BPH. However, metalloproteinase-2 and chemokine ligand 14 (CXCL14) were expressed at higher levels by fibroblasts from BPH. The fibroblastic growth factor-7 was highly expressed by CAFs from localized tumors, but metalloproteinase-11 in metastatic tumors. MMP-11, androgen receptor (AR) and heat-shock-70kda-protein-1A (HSPA1A) expressions were significantly higher in CAFs from CRPC. These results demonstrate a CAFs heterogeneity among prostate carcinomas with regard to some molecular profile expressions that may be relevant in tumor development (IL-17RB), progression (MMP-11) and castration resistance (AR, MMP-11 and HSPA1A).