Stromal factors involved in human prostate cancer development, progression and castration resistance
PurposeTo 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).Materials and methodsThe genomic expression of 20 stroma derived factors, including the androgen receptor (AR) growth factors (FGF2, FGF7, FGF10, HGF, TGFb, PDGFB) protein implicated in invasion (MMP 2, MMP 9 and MMP 11) inflammation (IL 6, IL 17, STAT 3 and NFkB) 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.ResultsFinally, 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.ConclusionsThese 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)
Journal of Cancer Research and Clinical Oncology