Effects of adrenal androgens on the transplantable human prostate tumor PC-82

Weerden, W.M. Van

doi:10.1210/en.131.6.2909

Cited by 9 publications

(5 citation statements)

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“…However, this effect was not observed after OVX. This can be explained by the fact that OVX not only abolishes the synthesis of estrogens but also the androgens, since the ovaries are the main source of androgens in female mice [ 36 ]. This is in contrast to human females where the adrenal cortex is the main source of androgens [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

et al. 2016

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Most lymphomas show higher incidence and poorer prognosis in males compared to females. However, the endocrine contribution to this gender difference is not entirely known. Here we show that castration accelerates lymphoma growth in C57BL6 male mice grafted with murine EG7 T cell lymphoma cells. However, the androgen receptor antagonist Bicalutamide did not affect lymphoma growth, suggesting no impact of androgen receptor signaling on lymphoma progression. In contrast, inhibition of androgen-to-estrogen conversion by the aromatase inhibitor (AI) Letrozole induced faster lymphoma growth in mice, suggesting that androgens impact lymphoma growth through its conversion to estrogens. This was supported by the inability of dihydrotestosterone, which is not converted to estrogens by aromatase, to influence lymphoma growth in castrated male mice. Lymphoma growth was also stimulated in immunocompromised mice grafted with human B cell lymphoma (Granta-519) and treated with either reversible or irreversible AIs, showing that the blockage of estrogen synthesis caused enhanced growth of both murine T and human B cell lymphomas and with different AIs. Additionally, AI-treated EG7 lymphomas showed accelerated growth not only in male but also in intact female mice. Altogether, our results demonstrate that aromatase inhibition accelerates lymphoma growth but not androgens per se, highlighting a protective role of estrogens in lymphoma pathogenesis. These results also raise concern that the use of AIs in women with breast cancer might enhance lymphoma progression.

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Section: Discussionmentioning

confidence: 99%

Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

et al. 2016

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“…This PDX was routinely passaged by subcutaneous grafting of small fragments into both shoulders of intact male athymic NMRI nu/nu mice (Taconic) under isoflurane anaesthesia. Mice were supplemented with self-made testosterone-containing silastic implants as described previously 24 .…”

Section: Methodsmentioning

confidence: 99%

Capturing complex tumour biology in vitro: histological and molecular characterisation of precision cut slices

Davies

Meng

Gutekunst

et al. 2015

Sci Rep

104

120

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Precision-cut slices of in vivo tumours permit interrogation in vitro of heterogeneous cells from solid tumours together with their native microenvironment. They offer a low throughput but high content in vitro experimental platform. Using mouse models as surrogates for three common human solid tumours, we describe a standardised workflow for systematic comparison of tumour slice cultivation methods and a tissue microarray-based method to archive them. Cultivated slices were compared to their in vivo source tissue using immunohistochemical and transcriptional biomarkers, particularly of cellular stress. Mechanical slicing induced minimal stress. Cultivation of tumour slices required organotypic support materials and atmospheric oxygen for maintenance of integrity and was associated with significant temporal and loco-regional changes in protein expression, for example HIF-1α. We recommend adherence to the robust workflow described, with recognition of temporal-spatial changes in protein expression before interrogation of tumour slices by pharmacological or other means.

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“…Mice produce very low levels of adrenal androgens; the castration environment is dissimilar to the human high levels of circulating adrenal androgens 61-63. Therefore, the mouse model to mimic human castration should be humanized by introducing and maintaining stable adrenal androgen levels prior to study.…”

Section: Perspectives and Challengesmentioning

confidence: 99%

Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

Fiandalo¹,

Wilton²,

Mohler³

2014

Int. J. Biol. Sci.

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Almost all men who present with advanced prostate cancer (CaP) and many men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to describe the evolution of adrenal androgen blockade, how new androgen measurement methods have furthered understanding of androgen metabolism, and how further understanding of the backdoor pathway of androgen metabolism may lead to interventions that extend survival even more.

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Effects of adrenal androgens on the transplantable human prostate tumor PC-82

Cited by 9 publications

References 0 publications

Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

Capturing complex tumour biology in vitro: histological and molecular characterisation of precision cut slices

Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

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