Organ culture of benign, aging, and hyperplastic human prostate

Pretlow, Thomas G.; Yang, Bin; Pretlow, Theresa P.

doi:10.1002/jemt.1070300403

Cited by 12 publications

(9 citation statements)

References 83 publications

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“…The low level of enzyme activity in organ culture may be of interest in light of the changes that occurred in prostate tissue over time in culture. These included a proliferative response in the basal epithelial cell population and a concomitant loss of the malignant component (Schrodt and Foreman, 1971;Geller et al, 1992;Nevalainen et al, 1993;Pretlow et al, 1995;Varani et al, 1999; as well as the present report). The present study also demonstrated migration of the proliferating epithelial cells out from the gland across the surface of the tissue.…”

Section: Discussionsupporting

confidence: 51%

Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: Levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue

et al. 2001

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Summary Prostate tissue was obtained from 22 radical prostatectomies (performed for clinical management of prostate carcinoma) immediately after surgery. A small piece of tissue was fixed immediately in formalin and used for routine histology while a second piece was frozen in OCT and used for immuno-histochemistry. Another small piece was used for isolation of epithelial and stromal cells. The remainder of the tissue was cut into 2 × 2 mm pieces and incubated in organ culture for 8 days. In organ culture, non-malignant, basal epithelial cells underwent a proliferative response. This was accompanied by de-differentiation of glandular structures and by migration of epithelial cells across the surface of the tissue. Erosion of the basement membrane could also be seen in places, but was not widespread. Invasion of epithelial cells into the adjacent stroma was not evident. Production of matrix metalloproteinases (MMPs) with gelatinolytic activity or collagenolytic activity was assessed in organ culture and compared to expression patterns in fresh tissue. MMP-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) were undetectable or low in fresh tissue specimens. Both enzymes were detected in organ culture and both increased over time. Even after 6 days, however, there was only a low level of gelatin-hydrolytic activity and no measurable collagenhydrolytic activity. In past studies we used organ cultures of normal skin and malignant skin tumours (basal cell carcinomas) to help elucidate the role of collagenolytic and gelatinolytic MMPs in epithelial cell invasion (Varani et al, 2000). Compared to MMP levels observed in skin, levels of these enzymes in prostate are low. The low level of collagenolytic and gelatinolytic MMPs in fresh prostate tissue and in organcultured prostate tissue may help explain why there is little tissue destruction in many primary prostate tumours and why the majority of such tumours remain confined to the prostate for extended periods. Although these past studies clearly indicate that several MMPs are elaborated in prostate tumours and suggest differences between malignant and non-malignant tissue, the heterogeneity in prostate tumour presentation and the variability in the analytical methods used make elucidating the relationship between enzyme elaboration and disease-state difficult to ascertain. Furthermore, the presence of active forms of the enzymes has not been established in these studies, and the biological significance of the reported differences is unclear. In the present study, a combination of approaches has been employed to assess expression of collagenolytic and gelatinolytic MMPs in prostate tissue removed for treatment of prostate carcinoma. We report here that gelatinolytic and collagenolytic MMPs can be detected in freshly isolated prostate tissue or in short-term (2-3 day) organ culture. Expression is heterogeneous from tissue to tissue, consistent with the variation in disease presentation. Expression patterns in fresh tissue and organ-cultured tissue also differ. E...

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Section: Discussionsupporting

confidence: 51%

Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: Levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue

et al. 2001

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“…1A). This method was selected for two key reasons: firstly, the use of a substrate for explant culture prevents cellular outgrowth that is frequently observed when tissues are cultured without support and completely submerged in media (Pretlow et al, 1995;Varani et al, 1999); secondly, the gelatin sponge used in this study is a commercial medical device developed for hemostasis (Ferrosan, 2014) that is readily available, cost-effective, and simple to use, making the method feasible for widespread adoption in translational cancer research laboratories. Figure 1A illustrates the PDE method using prostate tumors as an example.…”

Section: Pde Culture Of Solid Tumorsmentioning

confidence: 99%

“…(2013). Despite this long‐standing history and general acknowledgment of the potential of ex vivo cultured tissues to increase the clinical relevance of laboratory research (Centenera et al ., 2013; Kim, 2005; Pretlow et al ., 1995; Risbridger et al ., 2018; Vescio et al ., 1991), the PDE method has not been widely adopted to study solid tumors. The purpose of this study was to highlight advantages of the PDE model and demonstrate how it can be applied to interrogate hormone‐dependent cancers such as those of the breast and prostate.…”

Section: Introductionmentioning

confidence: 99%

“…Ex vivo culture of human prostatic tissue has been used since the 1970s with varying degrees of success, and protocols ranging from total immersion of tissue pieces in medium to culture of tissue pieces or slices on grid or sponge scaffolds, reviewed by Centenera et al (2013). Despite this long-standing history and general acknowledgment of the potential of ex vivo cultured tissues to increase the clinical relevance of laboratory research (Centenera et al, 2013;Kim, 2005;Pretlow et al, 1995;Risbridger et al, 2018;Vescio et al, 1991), the PDE method has not been widely adopted to study solid tumors. The purpose of this study was to highlight advantages of the PDE model and demonstrate how it can be applied to interrogate hormone-dependent cancers such as those of the breast and prostate.…”

Section: Introductionmentioning

confidence: 99%

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A patient‐derived explant (PDE) model of hormone‐dependent cancer

et al. 2018

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Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient‐derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient‐derived explants (PDEs), provides a high‐throughput and cost‐effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient‐derived material has high potential to facilitate implementation of personalized medicine approaches.

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“…Indeed, for a cultured tumor to be representative of actual cancer, it is essential that the tumor, as it proliferates in vitro, maintains its tissue organization and structure, its oncogenic properties, its differentiated functions, and any cellular heterogeneity present in vivo. All these requirements are fulfilled by prostate organ culture [13][14][15]. By adding lymphocyte stimuli in the culture medium, it is therefore possible to analyze T cell responsiveness in normal or tumor tissues (Fig.…”

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confidence: 99%