title: Stromal factors involved in human prostate cancer development, progression and castration resistance.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGFβ, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NFκB), 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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).
authors: Unidad de Investigación, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33920, Gijón, Asturias, Spain.
authors: Noemi
authors: N
authors: Eiro
authors: Unidad de Urología, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain.
authors: Jesus
authors: J
authors: Fernandez-Gomez
authors: Servicio de Urología, Fundación Hospital de Jove, Avda. Eduardo de Castro, 161, 33920, Gijón, Asturias, Spain.
authors: Raquel
authors: R
authors: Sacristán
authors: Unidad de Investigación, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33920, Gijón, Asturias, Spain.
authors: Belen
authors: B
authors: Fernandez-Garcia
authors: Unidad de Urología, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain.
authors: Beatriz
authors: B
authors: Lobo
authors: Unidad de Urología, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain.
authors: Jorge
authors: J
authors: Gonzalez-Suarez
authors: Unidad de Urología, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain.
authors: Alejandro
authors: A
authors: Quintas
authors: Unidad de Investigación, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33920, Gijón, Asturias, Spain.
authors: Safwan
authors: S
authors: Escaf
authors: Unidad de Investigación, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33920, Gijón, Asturias, Spain. investigacion@hospitaldejove.com.
authors: Francisco J
authors: FJ
authors: Vizoso
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D011944:Receptors, Androgen; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11
keywords: Androgen deprivation therapy; Cancer-associated fibroblasts (CAFs); Castration-resistant prostate cancer; Metastatic cancer; Tumor stroma