Laminin‐1 and α6β1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells

Deocampo, Daniel M.; Kleinman, Hynda K.; Deocampo, Nestor D.; Webber, Mukta M.

doi:10.1002/1097-0045(20010201)46:2<142::aid-pros1018>3.3.co;2-2

Cited by 30 publications

(38 citation statements)

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“…RWPE-1 cells undergo acinar-like morphogenesis with spherically arranged polarization and both structural and functional differentiation when grown in a 3D Matrigel environment (Bello-DeOcampo et al, 2001b). When RWPE-1 cells were transfected with control GL2-luciferase siRNA, they organized themselves into distinct acini 4 days after plating on Matrigel ( Figure 6A, a), similar to non-transfected cells (data not shown).…”

Section: Dkk-3 In Prostate Cell Growth and Morphogenesis Y Kawano Et Almentioning

confidence: 63%

“…Reduction of Dkk-3 expression in RWPE-1 cells resulted in a decrease in acinar size and a failure of acinar formation, suggesting that Dkk-3 is important for acinar development and/or differentiation. There are a number of crucial events necessary for normal acinar formation, including growth factor stimulation (Hoffman et al, 1996;Bello-DeOcampo et al, 2001b), cell-matrix interactions (Hoffman et al, 1996;Bello-DeOcampo et al, 2001a;Naylor et al, 2005) and cell-cell interactions (Hoffman et al, 1996;Menko et al, 2002). Experiments are underway to determine which of these is altered upon depletion of Dkk-3.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of prostate cell growth and morphogenesis by Dickkopf-3

et al. 2006

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Wnt signalling plays a critical role in the development of cancer. Recent studies indicate that Wnt signalling is negatively regulated by secreted Wnt antagonists such as secreted frizzled related proteins (sFRPs) and Dickkopfs (Dkks). We compared Dkk family expression levels in normal prostate and prostate cancer cells and found a reduction in Dkk-3 expression in cancer cells. Ectopic expression of Dkk-3 inhibited colony formation in LNCaP and PC3 prostate cancer cell lines and inducible expression of Dkk-3 reduced LNCaP cell proliferation. Moreover, small interfering RNAmediated downregulation of Dkk-3 enhanced cell cycle progression in untransformed RWPE-1 prostate epithelial cells. Immunohistochemical analysis revealed that Dkk-3 is expressed in a subset of normal prostate gland acini and that Dkk-3 expression is reduced in prostate tumours, particularly those with a high Gleason grade, suggesting a role for Dkk-3 in postmitotic differentiation. Consistent with this, depletion of Dkk-3 disrupted acinar morphogenesis of RWPE-1 cells in a threedimensional cell culture model. Our results are consistent with the loss of Dkk-3 expression resulting in impairment of glandular structure and uncontrolled prostate epithelial cell (PrEC) proliferation, both of which are crucial for prostate cancer progression.

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Section: Dkk-3 In Prostate Cell Growth and Morphogenesis Y Kawano Et Almentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Regulation of prostate cell growth and morphogenesis by Dickkopf-3

et al. 2006

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“…Although knockdown of TEAD1 or c-Cbl in RWPE1 did not affect proliferation in 2D culture, the ability of these cells to form acini in an established 3D assay (Bello-DeOcampo et al, 2001;Kawano et al, 2006) was compromised. These data suggest that TEAD1 and c-Cbl could have roles in regulating prostate epithelial cell differentiation and may have additional functions in epithelial morphogenesis, such as regulating adhesion to the basement membrane and associated signalling.…”

Section: Discussionmentioning

confidence: 91%

TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer

et al. 2008

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Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.

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“…Assays developed to measure neural and mammary stem cell self-renewal in vitro propagate these cells as spheres in an attempt to preserve their specialized biology (23,24). Several studies have shown that human prostate cells can form epithelial spheroids when cocultured with stromal cells and suspended in Matrigel in vitro (25)(26)(27). This strategy was adapted to develop a method for measuring murine prostate stem cell self-renewal.…”

Section: The Lsc Subpopulation Is Enriched For Sphere-forming Cells Withmentioning

confidence: 99%

Isolation and functional characterization of murine prostate stem cells

Lawson

Lukacs

et al. 2007

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

355

425

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The ability to isolate prostate stem cells is essential to explore their role in prostate development and disease. In vitro prostate colonyand sphere-forming assays were used to quantitatively measure murine prostate stem/progenitor cell enrichment and self-renewal. Cell surface markers were screened for their ability to positively or negatively enrich for cells with enhanced growth potential in these assays. Immunohistochemical and FACS analyses demonstrate that specific cell surface markers can be used to discriminate prostate stromal (CD34 ؉ ), luminal epithelial (CD24 ؉ CD49f ؊ ), basal epithelial (CD24 ؉ CD49f ؉ ), hematopoietic (CD45 ؉ , Ter119 ؉ ), and endothelial (CD31 ؉ ) lineages. Sorting for cells with a CD45 ؊ CD31 ؊ Ter119 ؊ Sca-1 ؉ CD49f ؉ antigenic profile results in a 60-fold enrichment for colony-and sphere-forming cells. These cells can self-renew and expand to form spheres for many generations and can differentiate to produce prostatic tubule structures containing both basal and luminal cells in vivo. These cells also localize to the basal cell layer within the region of the gland that is proximal to the urethra, which has been identified as the prostate stem cell niche. Prostate stem cells can be isolated to a purity of up to 1 in 35 by using this antigenic profile. The remarkable similarity in cell surface profile between prostate and mammary gland stem cells suggests these markers may be conserved among epithelial stem cell populations.CD49f ͉ integrin ␣6 ͉ Sca-1 ͉ CD24 heat-stable antigen ͉ stem cell niche S tem cells are of interest clinically because of their potential to repair damaged tissues, treat degenerative diseases, and because of their purported role in tumor initiation. The ability to identify and isolate stem cells is necessary to study their specialized biology. Enrichment for many types of tissue stem cells has been achieved by using cell surface markers. Murine hematopoietic stem cells can be enriched by sorting Lin Ϫ Thy-1 lo Sca-1 ϩ ckit ϩ cells from the bone marrow (1). Recent studies suggest that even better purity can be achieved by further sorting based on expression of the SLAM family receptors CD150 and CD48 (2). Bronchioavelolar stem cells can be isolated from their niche at the bronchioalveolar duct junction (BADJ) by sorting cells with a CD45 Ϫ CD31 Ϫ Sca-1 ϩ CD34 ϩ profile (3). Data from two recent reports show that mouse mammary stem cells possess a Lin Ϫ Sca-1 ϩ CD140a Ϫ CD24 ϩ CD49f ϩ CD29 ϩ cell surface profile and can be isolated to a purity of up to 1 in 20 by using subsets of these markers (4, 5).The presence of stem cells in the prostate first was proposed to explain the seemingly inexhaustible capacity of the organ to regenerate during androgen cycling experiments (6). The identification of side-population cells and replication quiescent BrdU label-retaining cells further suggests that stem cells exist in the gland (7,8). Several studies have enriched for primitive prostate cells by using cell surface markers. Richardson et al. (9) demonstrated that th...

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Laminin‐1 and α6β1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells

Cited by 30 publications

References 0 publications

Regulation of prostate cell growth and morphogenesis by Dickkopf-3

Regulation of prostate cell growth and morphogenesis by Dickkopf-3

TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer

Isolation and functional characterization of murine prostate stem cells

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