Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA

Zingiryan, Areg; Farina, Nicholas H.; Finstad, Kristiaan H.; Stein, Janet L.; Lian, Jane B.

doi:10.1002/jcp.25384

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…A total of 94 samples were selected for further RNAseq analysis, including 20 normal prostatic lobes as well as PIN and tumours from both mouse models (). In contrast to a recent publication reporting that high‐quality RNA can only be obtained from the lateral and ventral lobes (Zingiryan et al , ), we were able to obtain RNA with sufficient RNA quality from all lobes ().…”

Section: Resultsmentioning

confidence: 99%

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

Jurmeister¹,

Ramos-Montoya²,

Sandi³

et al. 2018

EMBO Mol Med

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Genetically engineered mouse models of cancer can be used to filter genome‐wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate cancer, PB‐Cre/PtenloxP/loxP and p53loxP/lox PRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer‐associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate cancer progression and was associated with biochemical recurrence.

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Section: Resultsmentioning

confidence: 99%

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

Jurmeister¹,

Ramos-Montoya²,

Sandi³

et al. 2018

EMBO Mol Med

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“…Successful inoculation of the mouse prostate may be achieved with an open surgery approach and the assistance of a surgical microscope [6,7]. Several orthotopic prostate cancer xenograft mouse models have been established by inoculating tumor cells into the anterior prostate (AP), as the anterior lobes are the largest and easiest to puncture [8].…”

Section: Introductionmentioning

confidence: 99%

Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate

Liu

Zhu

et al. 2022

BMC Cancer

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Background Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge. Methods Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described. Results The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n = 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma. Conclusions This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.

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“…The prostates were harvested from mice after euthanizing as described previously (32). Depending on the experimental design, each prostate sample (separated by lobes) were either fixed in 10% formalin or frozen @ −80°C in TRIzol TM reagent (Life Technologies Corporation, Grand Island, NY, USA), or frozen @ −80°C in 1X RIPA (Santa Cruz Biotechnology, Dallas, TX, USA) containing complete EDTA protease inhibitor cocktail and phosSTOP phosphatase inhibitor (Millipore-Sigma, Burlington, MA, USA), or processed for tissue digestion for flow cytometry as described below.…”

Section: Methodsmentioning

confidence: 99%

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

Pattabiraman

Bell-Cohn

Murphy

et al. 2021

Preprint

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Intraurethral inoculation of mice with uropathogenic E. coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and in CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells and the histamine 1 receptor in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain (MLC)-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW AND NOTEWORTHYLUTS-associated BPH is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.

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Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA

Cited by 12 publications

References 14 publications

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

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