A comparative study of the ultrastructure and lack of growth capacity of adult human prostate epithelium mechanically separated from its stroma

Franks, L. M.; Riddle, P. R.; Carbonell, A. W.; Gey, G. O.

doi:10.1002/path.1711000206

Cited by 135 publications

(46 citation statements)

References 24 publications

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“…Following the observation that epithelium loses its growth capacity when separated from the stroma (Franks et al, 1970), it has become increasingly clear that both autocrine and paracrine factors produced by epithelial and stromal cells play an important role in the local control of prostatic growth. It has been demonstrated that urogenital sinus mesenchyme plays a major role in the (androgen-induced) development of the gland (Cunha et al, 1987); subsequently it was shown that these interactions may have retained their integral role in the adult prostate (Cunha et al, 1987;Chung et al,1991a,b (Thompson, 1990;Story, 1991), and some of these have been positively identified as being produced (also) by stromal cells, suggesting a role in stromal-epithelial interactions (Story et al, 1989;Djakiew et al, 1991;Gleave et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Kooistra

Raaij²,

Klaij³

et al. 1995

Br J Cancer

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Summary The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Stromal cells from the human prostate have previously been shown to inhibit anchoragedependent as well as anchorage-independent growth of the prostatic tumour epithelial cell lines PC-3 and LNCaP. Antiproliferative activity, mediated by a diffusible factor in the stromal cell conditioned medium, was found to be produced specifically by prostatic stromal cells. In the present study the characteristics of this factor were examined. It is demonstrated that prostate stroma-derived inhibiting factor is an acid-and heat-labile, dithiothreitol-sensitive protein. Although some similarities with type beta transforming growth factor (TGF-P)-like inhibitors are apparent, evidence is presented that the factor is not identical to TGF-J3 or to the TGF-p-like factors activin and inhibin. Absence of TGF-P activity was shown by the lack of inhibitory response of the TGF-p-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated, partially purified preparations of the inhibitor. Furthermore, neutralising antibodies against TGF-PI or TGF-P2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. Using Northern blot analyses, we excluded the involvement of inhibin or activin. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.

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Section: Discussionmentioning

confidence: 99%

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Kooistra

Raaij²,

Klaij³

et al. 1995

Br J Cancer

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“…In contrast, malignant tumors are undifferentiated and exhibit no apparent relationship between epithelial and stromal cells (15). Mesenchyme plays an active role in growth and differentiation of the epithelium during prostate development (4,6), and the stroma has been implicated in maintenance of adult epithelium (5,9). However, the role of the stroma in development and progression of tumors has received less attention.…”

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confidence: 99%

Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy.

Yan¹,

Fukabori²,

Mcbride³

et al. 1993

Mol. Cell. Biol.

377

316

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Stroma and the heparin-binding fibroblast growth factor (FGF) family influence normal epithelial cell growth and differentiation in embryonic and adult tissues. The role of stromal cells and the expression of isoforms of the FGF ligand and receptor family were examined during malignant progression of epithelial cells from a differentiated, slowly growing, nonmalignant model rat prostate tumor. In syngeneic hosts, a mixture of stromal and epithelial cells resulted in nonmalignant tumors which were differentiated and slowly growing.In the absence of the stromal cells, epithelial cells progressed to malignant tumors which were independent of the stroma and undifferentiated. The independence of the malignant epithelial cells from stromal cells was accompanied by a switch from exclusive expression of exon Illb to exclusive expression of exon IlIc in the FGF receptor 2 (FGF-R2) gene. The FGF-R2(IIIb) isoform displays high affinity for stromal cell-derived FGF-7, whereas the FGF-R2(Ic) isoform does not recognize FGF-7 but has high affinity for the FGF-2 member of the The development of prostate tumors is age related and believed to progress by a series of genetic changes and selection of cells with increasing malignant character. Most marked is the shift from relatively slowly growing, nonmetastatic, androgen-sensitive tumors to a rapidly growing, androgen-independent, highly malignant stage (15). The androgen-sensitive tumors are subject to antiandrogen therapies which can result in regression of the tumor, but frequently appearance of a highly malignant tumor that is resistant to treatment follows such therapies. A lack of knowledge of mechanisms underlying the appearance of the malignant tumors has hampered design of strategies for prediction and prevention of their appearance as well as intervention after they appear. The epithelial cell compartment of slowly growing, androgen-sensitive tumors usually exhibits some degree of morphological differentiation that distinguishes it from the stromal compartment. In contrast, malignant tumors are undifferentiated and exhibit no apparent relationship between epithelial and stromal cells (15). Mesenchyme plays an active role in growth and differentiation of the epithelium during prostate development (4, 6), and the stroma has been implicated in maintenance of adult epithelium (5, 9). However, the role of the stroma in development and progression of tumors has received less attention. Advances in isolation and maintenance of specific prostate cell types in vitro and the identification of purified * Corresponding author. t Present address: Department of Urology, Gunma University, Maebashi, Gunma 371, Japan. polypeptide regulators that act directly on them has renewed optimism for understanding the cellular and molecular basis of the progression of prostate tumors (25,(27)(28)(29)(30)39). Isolated epithelial and stromal cells from both normal prostate tissue and slowly growing, androgen-sensitive tumors are insensitive to androgen, yet they are responsive to multiple polypeptid...

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“…Trypsin, collagenase, and DNAseI, alone or in combination, are most commonly used for this purpose. For the collagen-rich prostate tissue, collagenase disaggregation has long since been the method of choice to obtain highly viable cell suspensions that are able to proliferate in vitro (5,18,21). This enzyme has therefore also been used to prepare prostate tumor cell suspensions for the initiation of short-term tissue cultures for cytogenetic analysis (3,13).…”

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confidence: 99%

Preferential loss of abnormal prostate carcinoma cells by collagenase treatment

König¹,

Dongen²,

Schröder³

1993

Cytometry

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Effects of two different methods of tumor disaggregation on flow cytometric ploidy distribution and intact cell yield were investigated. Either mechanical disaggregation or collagenase digestion was applied to 35 prostate tumor specimens. Seven collagenase-treated samples failed to yield any intact cells, whereas with mechanical disaggregation in all cases a sufficient number of intact cells were obtained. No differences in the FCM ploidy distribution of tumors with a DNA diploid stemline were observed comparing both techniques. In DNA aneuploid tumors, however, collagenase treatment had an adverse effect on the abnormal cell populations. In 14/17 of such tumors, the abnormal cell populations were significantly reduced; in eight of these the percentage of DNA aneuploid cells declined even below the minimum percentage (10%) that was defined for DNA aneuploidy. Since collagenase is a widely used enzyme for tissue disaggregation, especially in tumor cytogenetics, the presented data will have consequences for the interpretation of results obtained by methods involving the use of this enzyme.

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A comparative study of the ultrastructure and lack of growth capacity of adult human prostate epithelium mechanically separated from its stroma

Cited by 135 publications

References 24 publications

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy.

Preferential loss of abnormal prostate carcinoma cells by collagenase treatment

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