PMID- 23589051
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20151119
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 42
IP  - 6
DP  - 2013 Jun
TI  - Phenotypic characterization of human prostatic stromal cells in primary cultures 
      derived from human tissue samples.
PG  - 2116-22
LID - 10.3892/ijo.2013.1892 [doi]
AB  - Emerging evidence has shown that the tumor microenvironment plays a crucial role 
      in prostate cancer (PCa) development and progression. However, the mechanism(s) 
      through which stromal cells regulate epithelial cells and the differences among 
      prostatic stromal cells of different histological/pathological origin in PCa 
      progression remain unclear. Therefore, it is necessary to characterize the 
      stromal cell populations present in benign prostatic hyperplasia (BPH) and PCa. 
      To this end, we used cultures from stromal cells obtained from BPH-derived (15 
      cases) and PCa-derived (30 cases) primary cultures. In culture, stromal cells are 
      a mixture of fibroblasts, myofibroblasts (MFs) and muscle cells. Fibroblasts are 
      characterized for the expression of vimentin, MFs for the co-expression of 
      alpha-smooth muscle actin (alpha-SMA) and vimentin, whereas muscle cells for the 
      expression of alpha-SMA and desmin. Fibroblasts were present in large amounts in the 
      BPH- compared to the PCa-derived cultures, whereas MFs were more representative 
      of PCa- as opposed to BPH-derived cultures. Some alpha-SMA-positive cells retained 
      the expression of basal cytokeratin K14. This population was defined as 
      myoepithelial cells and was associated with senescent cultures. The percentage of 
      MFs was higher in high-grade compared to moderate- and low-grade PCa-derived 
      cultures, whereas the number of myoepithelial cells was lower in high-grade 
      compared to moderate- and low-grade PCa-derived cultures. In addition, we 
      analyzed the expression of p75NTR, as well as the expression of matrix 
      metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of MMPs (TIMPs). p75NTR 
      expression was elevated in the stromal cultures derived from PCa compared to 
      those derived from BPH and in cultures derived from cases with Gleason scores >/=7 
      compared to those derived from cases with Gleason scores <7, as well as in 
      cultures with a high concentration of MFs compared to those with a high 
      concentration of fibroblasts. MMP-2 was secreted by all primary cultures, whereas 
      MMP-9 secretion was observed only in some PCa-derived stromal cells, when the 
      percentage of MFs was significantly higher compared to BPH-derived cultures. 
      TIMP1, TIMP2 and TIMP3 were secreted in elevated amounts in the BPH- compared to 
      the PCa-derived stromal cultures, suggesting the differential regulation of 
      extracellular matrix (ECM) degradation. When we used 22rv1 and PC3 PCa xenograft 
      models for the isolation and characterization of murine cancer-associated 
      fibroblasts (CAFs) we noted that the angiogenic wave was concurrent with the 
      appearance of a reactive stroma phenotype, as determined by staining for alpha-SMA, 
      vimentin, tenascin, calponin, desmin and Masson's trichrome. In conclusion, MF 
      stromal cells from PCa participate in the progression and metastasis of PCa, 
      modualting inflammation, angiogenesis and epithelial cancer cell proliferation.
FAU - Gravina, Giovanni Luca
AU  - Gravina GL
AD  - Department of Biotechnological and Applied Clinical Sciences, Laboratory of 
      Radiobiology, University of L'Aquila, L'Aquila, Italy.
FAU - Mancini, Andrea
AU  - Mancini A
FAU - Ranieri, Guido
AU  - Ranieri G
FAU - Di Pasquale, Boris
AU  - Di Pasquale B
FAU - Marampon, Francesco
AU  - Marampon F
FAU - Di Clemente, Luigi
AU  - Di Clemente L
FAU - Ricevuto, Enrico
AU  - Ricevuto E
FAU - Festuccia, Claudio
AU  - Festuccia C
LA  - eng
PT  - Journal Article
DEP - 20130410
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (ACTA2 protein, human)
RN  - 0 (Actins)
RN  - 0 (Biomarkers)
RN  - 0 (Desmin)
RN  - 0 (Keratin-14)
RN  - 0 (NGFR protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Vimentin)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Actins/metabolism
MH  - Biomarkers/metabolism
MH  - Cell Proliferation
MH  - Desmin/metabolism
MH  - Fibroblasts/metabolism/pathology
MH  - Humans
MH  - Keratin-14/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Neovascularization, Pathologic
MH  - Nerve Tissue Proteins/metabolism
MH  - Phenotype
MH  - Prostatic Hyperplasia/metabolism/*pathology
MH  - Prostatic Neoplasms/metabolism/*pathology
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Stromal Cells/*metabolism/*pathology
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Tumor Cells, Cultured
MH  - Vimentin/metabolism
EDAT- 2013/04/17 06:00
MHDA- 2013/12/24 06:00
CRDT- 2013/04/17 06:00
PHST- 2012/09/27 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/04/17 06:00 [entrez]
PHST- 2013/04/17 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
AID - 10.3892/ijo.2013.1892 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Jun;42(6):2116-22. doi: 10.3892/ijo.2013.1892. Epub 2013 Apr 
      10.