Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells

Webber, Mukta M.; Bello, Diana; Kleinman, Hynda K.; Hoffman, Matthew P.

doi:10.1093/carcin/18.6.1225

Cited by 118 publications

(97 citation statements)

References 10 publications

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“…These interactions involve insoluble extracellular matrix, stroma consisting of fibroblast, adipose, vasculature, and resident immune cells as well as the conventional milieu of cytokines and growth factors (18). As a result of an alteration in these interactions, changes in the tissue organization are observed in many epithelial cancers including invasive prostatic carcinomas (19). The ability to form acinar structure was shown for low tumorigenic breast epithelial cells, whereas more malignant cells grew as chaotic clusters.…”

Section: Discussionmentioning

confidence: 99%

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Romanov¹,

Whyard²,

Adler³

et al. 2004

Cancer Research

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Bone metastasis is the most frequent complication of prostate cancer (PC). Elucidation of the biological basis of this specificity is required for the development of approaches for metastatic inhibition. We investigated the possibility that the preferential attachment of PC cells to bone marrow endothelium (as opposed to endothelium from other organs) affects this specificity. We selected, from peptide phage-displayed libraries, peptide ligands to surfaces of PC cells (C4-2B) attenuated (30 -40%) binding of C4-2B cells to bone marrow endothelial cells (BMECs). We then determined the molecules on the surface of C4-2B cells interacted with the selected peptides using column affinity chromatography and a cDNA expression phage-displayed library generated from C4-2B cells in T7 phage. We identified a phage from the cDNA library that specifically bound to one of the selected peptides-L11. This phage displayed the amino acid sequence homologous for the COOH-terminal portion of prostatespecific antigen (PSA). To examine the possible direct involvement of PSA in the interactions between PC and BMECs, we performed a cell-cell adhesion assay. Antibodies to PSA attenuated PC cells adhesion to BMECs. In addition, exogenous proteolytically active PSA modulated this adhesion. Finally, inactivation of mRNA coding PSA by a small interfering RNA (siRNA) diminished C4-2B cell adhesion to BMECs. These results indicate that PSA expressed as secreted and surface-associated molecules in C4-2B cells is involved in cell-cell interactions and/or digests components of bone marrow endothelium for preferential adhesion and penetration of PC cells. The suggested experimental approach is a promising strategy for identification of cell surface molecules involved in intercellular interactions.

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Section: Discussionmentioning

confidence: 99%

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Romanov¹,

Whyard²,

Adler³

et al. 2004

Cancer Research

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“…The non-cancerous cells were characterized by formation of acini (cell clusters), which resemble in vivo structures of prostate epithelial cells. Cancer prostate cells showed lack of organization and increased invasiveness, which is associated with cancer aggressiveness (Webber et al 1997). Matrigel constituent proteins promote cell-matrix interactions, affecting cell proliferation and differentiation.…”

Section: Multicellular Tumour Spheroids As a Primary 3d Tumour Modelmentioning

confidence: 99%

3D tumour models: novel in vitro approaches to cancer studies

Nyga

Cheema

Loizidou

2011

J. Cell Commun. Signal.

354

313

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3D in vitro models have been used in cancer research as a compromise between 2-dimensional cultures of isolated cancer cells and the manufactured complexity of xenografts of human cancers in immunocompromised animal hosts. 3D models can be tailored to be biomimetic and accurately recapitulate the native in vivo scenario in which they are found. These 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Approaches to create more biomimetic 3D models of cancer include, but are not limited to, (i) providing the appropriate matrix components in a 3D configuration found in vivo, (ii) coculturing cancer cells, endothelial cells and other associated cells in a spatially relevant manner, (iii) monitoring and controlling hypoxia-to mimic levels found in native tumours and (iv) monitoring the release of angiogenic factors by cancer cells in response to hypoxia. This article aims to overview current 3D in vitro models of cancer and review strategies employed by researchers to tackle these aspects with special reference to recent promising developments, as well as the current limitations of 2D cultures and in vivo models. 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Here we review current strategies in the field of modelling cancer, with special reference to advances in complex 3D in vitro models.

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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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Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells

Cited by 118 publications

References 10 publications

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

Prostate Cancer Cell Adhesion to Bone Marrow Endothelium

3D tumour models: novel in vitro approaches to cancer studies

Isolation and functional characterization of murine prostate stem cells

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