Are primary cultures realistic models of prostate cancer?

Peehl, Donna M.

doi:10.1002/jcb.10691

Cited by 40 publications

(31 citation statements)

References 74 publications

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“…However, ex vivo gene transfection to DCs is technically challenging (46). On the other hand, gene transfection into tumor cells is also difficult because of the need to culture tumor cells from each patient (47). Compared with these time-and laborconsuming methods, utilizing non-immune non-tumor cells as the target of gene transfection and the signal delivery carrier may provide a more efficient and realistic clinical use, if it has comparable efficacy to other methods.…”

Section: Discussionmentioning

confidence: 99%

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

Matsumura

Mandai²,

Hamanishi³

et al. 2008

Oncol Rep

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Abstract. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L) has been considered to be a major route of delivery for tumor immunotherapy because expression of its receptor, FLT3, was detected predominantly in hematopoetic progenitor cells. However, several studies indicate that FLT3L locally overexpressed in tumor or dendritic cells (DCs) also shows an anti-tumor effect. In the current study, we found that FLT3 expression is not present in monocytes but is instead induced in DCs through the differentiation process resulting from stimulation by GM-CSF and IL-4. Addition of FLT3L further augmented FLT3 induction and also increased CD40 expression in DCs, leading to enhanced induction of lymphoblastoid cell line-targeted cytotoxic Tlymphocyte response and CD107a mobilization in CD8 + T cells. Furthermore, FLT3L also induced FLT3 expression in peripheral blood NK cells that showed an enhanced response detected by CD107a mobilization. In a murine ovarian cancer model, locally expressed FLT3L showed anti-tumor effects. Collectively, the current study indicates that FLT3L has an immunostimulatory effect on peripheral blood cells and FLT3L targeted to mature peripheral blood cells may serve as a useful tool for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

Matsumura

Mandai²,

Hamanishi³

et al. 2008

Oncol Rep

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show abstract

“…Only 1 of 8 samples (N1) of normal prostate (surgically removed because of bladder carcinoma) grew in culture, whereas we successfully derived two cell strains from benign prostatic hyperplasia (C10 and C17) and one from a contralateral normal tissue characterized by the presence of prostate intraepithelial neoplasia (C16sx). Cultures from normal/hyperplastic tissue (N1, C10, C17, and C16sx) and cancer had similar growth rate (10,11). Importantly, all cultures had limited life span (20-25 population doublings) and similar cell morphology, as described (12).…”

Section: Isolation Of Prostate Epithelial Culturesmentioning

confidence: 91%

Epithelial-Restricted Gene Profile of Primary Cultures from Human Prostate Tumors: A Molecular Approach to Predict Clinical Behavior of Prostate Cancer

Nanni¹,

Priolo

Grasselli

et al. 2006

Molecular Cancer Research

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“…Tissues dissected from radical prostatectomy specimens were processed for primary culture of prostatic epithelial cells according to previously described methods (Peehl, 2004). None of the patients had received prior chemical, hormonal or radiation therapy.…”

Section: Primary Culturesmentioning

confidence: 99%

Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells

et al. 2004

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We hypothesized that key antiproliferative target genes for the vitamin D receptor (VDR) were repressed by an epigenetic mechanism in prostate cancer cells resulting in apparent hormonal insensitivity. To explore this possibility, we examined nuclear receptor corepressor expression in a panel of nonmalignant and malignant cell lines and primary cultures, and found frequently elevated SMRT corepressor mRNA expression often associated with reduced sensitivity to 1a,25-dihydroxyvitamin D 3 (1a,25(OH) 2 D 3 ). For example, PC-3 and DU-145 prostate cancer cell lines had 1.8-fold and twofold increases in SMRT mRNA relative to normal PrEC cells (Po0.05). Similarly, 10/15 primary tumour cultures (including three matched to normal cells from the same donors) had elevated SMRT mRNA levels; generally NCoR1 and Alien were not as commonly elevated. Corepressor proteins often have associated histone deacetylases (HDAC) and reflectively the antiproliferative action of 1a,25(OH) 2 D 3 can be 'restored' by cotreatment with low doses of HDAC inhibitors such as trichostatin A (TSA, 15 nM) to induce apoptosis in prostate cancer cell lines. To decipher the transcriptional events that lead to these cellular responses, we undertook gene expression studies in PC-3 cells after cotreatment of 1a,25(OH) 2 D 3 plus TSA after 6 h. Examination of known VDR target genes and cDNA microarray analyses revealed cotreatment of 1a,25(OH) 2 D 3 plus TSA cooperatively upregulated eight (outof1176)genes,includingMAPK-APK2andGADD45a. MRNA and protein time courses and inhibitor studies confirmed these patterns of regulation. Subsequently, we knocked down SMRT levels in PC-3 cells using a small interfering RNA (siRNA) approach and found that GADD45a induction by 1a,25(OH) 2 D 3 alone became very significantly enhanced. The same distortion of gene responsiveness, with repressed induction of GADD45a was found in primary tumour cultures compared and to matched peripheral zone (normal) cultures from the same donor. These data demonstrate that elevated SMRT levels are common in prostate cancer cells, resulting in suppression of target genes associated with antiproliferative action and apparent 1a,25(OH) 2 D 3 -insensitivity. This can be targeted therapeutically by combination treatments with HDAC inhibitors.

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Are primary cultures realistic models of prostate cancer?

Cited by 40 publications

References 74 publications

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

Epithelial-Restricted Gene Profile of Primary Cultures from Human Prostate Tumors: A Molecular Approach to Predict Clinical Behavior of Prostate Cancer

Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells

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