Differentiation of Human Prostate Cancer PC-3 Cells Induced by Inhibitors of Inosine 5′-Monophosphate Dehydrogenase

Floryk, Daniel; Tollaksen, Sandra L.; Giometti, Carol S.; Huberman, Eliezer

doi:10.1158/0008-5472.can-04-1553

Cited by 42 publications

(43 citation statements)

References 46 publications

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“…The differentiation of PC-3 prostatic cancer cells induced by mycophenolic acid, an inhibitor of 5 0 -monophosphate dehydrogenase, has been shown to involve the formation of cytoplasmic vesicles (Floryk and Huberman, 2005), and this kind of vesicle has been associated with the formation of an intracellular canal resembling early differentiation of the epithelium (Floryk et al, 2004). Indeed, we observed relatively large vesicles in the cytoplasm of nondifferentiated epi- 0 ,6-diamidine-2-phenylidole-dihydrochloride (DAPI) staining was used to identify nuclear compaction and fragmentation in the epithelium during lumen formation.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of the Epithelium During Canalization of the Rat Ventral Prostate

Bruni‐Cardoso

Carvalho

2007

The Anatomical Record

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Outgrowth and branching of solid cords are the initial events in postnatal prostatic morphogenesis. These processes involve cell proliferation and their projection into the stroma and precede epithelial canalization. The purpose of the present study was to examine the dynamics of the prostate epithelium during canalization of the rat ventral prostate in the first week of postnatal development using histological, stereological, and ultrastructural analyses. The terminal deoxynucleotidyltransferase [TdT]-mediated deoxy-UTP nick end labeling assay was used to investigate the occurrence of DNA fragmentation. Our results demonstrate that canalization of the prostate epithelium starts as early as on day 1 (24 hr after birth) and progresses thereafter. By the end of the first week (day 6), luminal volume density reached 3% (P < 0.05) of the organ. Canalization was the result of epithelial cell differentiation and apoptosis. The former involved organization of the epithelial cells into a single layer sitting on the basement membrane, polarization, enlargement of secretory organelles and accumulation of secretory vesicles, microvilli formation, and establishment of the adult pattern of cell junctions. The latter was observed to occur mostly to epithelial cells not in contact with the basement membrane. Structures of variable electron density were observed in the developing lumen. In conclusion, different phenomena seem to be involved in the canalization of the rat ventral prostate. However, it was evident from the present results that complex epithelial cell fate decisions take place during this process.

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Section: Discussionmentioning

confidence: 99%

Dynamics of the Epithelium During Canalization of the Rat Ventral Prostate

Bruni‐Cardoso

Carvalho

2007

The Anatomical Record

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“…Also, neoplastic prostate cells-even poorly differentiated prostate cancer metastases-have the capacity to synthesize and export prostasomes, but the altered tissue architecture in malignancy facilitates the release of prostasomes to the interstitial space rather than to the lumen of the prostate (25)(26)(27).…”

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Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

Tavoosidana

Ronquist

Darmanis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

209

173

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Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

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“…6) MPA has potential anti-cancer activity, and numerous studies have appeared in the literature. [7][8][9][10] Due to its apoptotic properties, 1 has entered phase I clinical trials in advanced multiple myeloma patients. 11,12) Dynamic histone acetylation and deacetylation exhibit a critical regulatory function on gene expression through an effect on nucleosome conformation.…”

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confidence: 99%