In Vivo Models for Prostate Cancer Research

Adamiecki, Robert; Hryniewicz-Jankowska, Anita; Ortiz, María A.; Li, Xiang; Porter-Hansen, Baylee A.; Nsouli, Imad; Bratslavsky, Gennady; Kotula, Leszek

doi:10.3390/cancers14215321

Cited by 6 publications

(5 citation statements)

References 133 publications

(177 reference statements)

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“…Thus, mechanisms governing splicing are likely cell-context-specific Multiple animal models of cancer have been developed, but surprisingly, there is little information on AR-SVs in these models. The best studies are PCa models developed by genetically engineering mice (reviewed [57]). Many models of aggressive cancer are representative of neuroendocrine malignancies and do not express AR.…”

Section: Classification and Signalingmentioning

confidence: 99%

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

2023

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Multiple studies have demonstrated the importance of androgen receptor (AR) splice variants (SVs) in the progression of prostate cancer to the castration-resistant phenotype and their utility as a diagnostic. However, studies on AR expression in non-prostatic malignancies uncovered that AR-SVs are expressed in glioblastoma, breast, salivary, bladder, kidney, and liver cancers, where they have diverse roles in tumorigenesis. AR-SVs also have roles in non-cancer pathologies. In granulosa cells from women with polycystic ovarian syndrome, unique AR-SVs lead to an increase in androgen production. In patients with nonobstructive azoospermia, testicular Sertoli cells exhibit differential expression of AR-SVs, which is associated with impaired spermatogenesis. Moreover, AR-SVs have been identified in normal cells, including blood mononuclear cells, neuronal lipid rafts, and the placenta. The detection and characterization of AR-SVs in mammalian and non-mammalian species argue that AR-SV expression is evolutionarily conserved and that AR-SV-dependent signaling is a fundamental regulatory feature in multiple cellular contexts. These discoveries argue that alternative splicing of the AR transcript is a commonly used mechanism that leads to an expansion in the repertoire of signaling molecules needed in certain tissues. Various malignancies appropriate this mechanism of alternative AR splicing to acquire a proliferative and survival advantage.

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Section: Classification and Signalingmentioning

confidence: 99%

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

2023

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“…To support the findings of carcinogen-induced prostate cancer mouse model in a more informative and conclusive manner, an additional pharmacodynamic experiment was performed on LNCaP 3D tumor spheroid model. Tumor spheroid is a 3D model with accurate physicochemical environment that is comparable to in vivo conditions (Adamiecki et al 2022;Volpatti and Yetisen 2014).…”

Section: Efficacy Of Apt-abr-np On Lncap Tumor Spheroid Modelmentioning

confidence: 99%

ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation

Al Hoque,

Dutta,

Paul

et al. 2023

Cancer Nano

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Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstract

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“…In a study by Barbieri et al [ 69 ], chromodomain-helicase DNA-binding protein 1 (CHD1) deletion and forkhead box protein (FOX) A1 and speckle-type POZ protein (SPOP) mutations were not detected in PCa cell lines, although these genetic changes were detected in PCa patients. Given these discoveries, the application of small mammalian animal models in cancer studies has become a promising alternative for assessing CRPC due to the accessibility of numerous mouse strains with specific gene modifications [ 70 ]. A number of in vivo tumour propagation models, such as genetically engineered mouse (GEM) models, patient-derived xenograft (PDX) models, and 3D cultures of patient-derived PC cells (organoid or sphere cultures), have been established by researchers to circumvent the restrictions of PCa cell lines [ 71 ].…”

Section: Roles Of Erα and Erβ In Castration-resistant Prostate Cancermentioning

confidence: 99%

The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches

et al. 2023

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Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERβ functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERβ in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERβ in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.

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In Vivo Models for Prostate Cancer Research

Cited by 6 publications

References 133 publications

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation

The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches

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