Xenograft, Transgenic, and Knockout Models of Prostate Cancer

Gaupel, Ann-Christin; Wang, Wei-Lin Winnie; Mordan-McCombs, Sarah; Lee, Edmund Chun Yu; Tenniswood, Martin

doi:10.1016/b978-0-12-415894-8.00039-7

Cited by 5 publications

(3 citation statements)

References 164 publications

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“…This effect could, in part, be attributed to the p53 status of these cell lines because this protein is one of the key molecules involved in a cell response to ionizing radiation [ 81 ]. The LNCaP C4-2 cells are p53-positive [ 82 ], while in contrast, the DU-145 cells are p53-mutant cells [ 83 ]. There are a number of papers covering the role that the p53 plays in determining the fate of solid tumor-derived cells after exposure to ionizing radiation, leading to the conclusion that loss of p53 function is responsible for radioresistance [ 84 , 85 , 86 ].…”

Section: Resultsmentioning

confidence: 99%

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy–Part I

et al. 2020

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Prostate cancer is the second most frequent malignancy in men worldwide. Unfortunately, current therapies often lead to the onset of metastatic castration-resistant prostate cancer (mCRPC), causing significant mortality. Therefore, there is an urgent need for new and targeted therapies that are advantageous over the current ones. Recently, the PSMA-targeted radioligand therapy of mCRPC has shown very promising results. In line with this, we described the synthesis of a new radioimmunoconjugate, 223RaA-silane-PEG-D2B, for targeted mCRPC therapy. The new compound consists of a NaA zeolite nanocarrier loaded with the α-particle emitting Ra-223 radionuclide, functionalized with the anti-PSMA D2B antibody. Physicochemical properties of the synthesized compound were characterized by standard methods (HR-SEM, TEM, XRD, FTIR, EDS, NTA, DLS, BET, TGA). The targeting selectivity, the extent of internalization, and cytotoxicity were determined in LNCaP C4-2 (PSMA+) and DU-145 (PSMA-) cells. Our results supported the 223RaA-silane-PEG-D2B synthesis and revealed that the final product had a diameter ca. 120 nm and specific activity 0.65 MBq/1mg. The product was characterized by a high yield of stability (>95% up to 12 days). The conjugation reaction resulted in approximately 50 antibodies/nanoparticle. The obtained radioimmunoconjugate bound specifically and internalized into PSMA-expressing LNCaP C4-2 cells, but not into PSMA-negative DU-145 cells. 223RaA-silane-PEG-D2B demonstrated also potent cytotoxicity in LNCaP C4-2 cells. These promising results require further in vivo evaluation of 223RaA-silane-PEG-D2B with regard to its toxicity and therapeutic efficacy.

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Section: Resultsmentioning

confidence: 99%

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy–Part I

et al. 2020

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“…Collectively, these are unique in vivo and in vitro models to study the mechanism of castration resistance. [ 133 ]. Later, several cell lines such as LuCaP 23.12, LuCaP 23.8, LuCaP 35, LuCaP 41, LuCaP 49, LuCaP 58, and LuCaP 73 were developed.…”

Section: Prostate Cancer Research Modelsmentioning

confidence: 99%

Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research

Saranyutanon

Deshmukh

Dasgupta

et al. 2020

Cancers

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We have witnessed noteworthy progress in our understanding of prostate cancer over the past decades. This basic knowledge has been translated into efficient diagnostic and treatment approaches leading to the improvement in patient survival. However, the molecular pathogenesis of prostate cancer appears to be complex, and histological findings often do not provide an accurate assessment of disease aggressiveness and future course. Moreover, we also witness tremendous racial disparity in prostate cancer incidence and clinical outcomes necessitating a deeper understanding of molecular and mechanistic bases of prostate cancer. Biological research heavily relies on model systems that can be easily manipulated and tested under a controlled experimental environment. Over the years, several cancer cell lines have been developed representing diverse molecular subtypes of prostate cancer. In addition, several animal models have been developed to demonstrate the etiological molecular basis of the prostate cancer. In recent years, patient-derived xenograft and 3-D culture models have also been created and utilized in preclinical research. This review is an attempt to succinctly discuss existing information on the cellular and molecular progression of prostate cancer. We also discuss available model systems and their tested and potential utility in basic and preclinical prostate cancer research.

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“…LNCaP cells have a mutation in their AR (T877A) which renders the receptor promiscuous to progesterone, estrogen and the antiandrogen bicalutamide (28). 22RV1 express a number of known AR variants associated with androgen independence (29). DU145 cells are AR negative and do not respond to androgens.…”

Section: Methodsmentioning

confidence: 99%

Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2

et al. 2019

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Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), yet many patients relapse with lethal metastatic disease. With this loss of androgens, increased cell plasticity has been observed as an adaptive response to ADT. This includes gain of invasive and migratory capabilities, which may contribute to PCa metastasis. Hyperinsulinemia, which develops as a side-effect of ADT, has been associated with increased tumor aggressiveness and faster treatment failure. We investigated the direct effects of insulin in PCa cells that may contribute to this progression. We measured cell migration and invasion induced by insulin using wound healing and transwell assays in a range of PCa cell lines of variable androgen dependency (LNCaP, 22RV1, DuCaP, and DU145 cell lines). To determine the molecular events driving insulin-induced invasion we used transcriptomics, quantitative real time-PCR, and immunoblotting in three PCa cell lines. Insulin increased invasiveness of PCa cells, upregulating Forkhead Box Protein C2 (FOXC2), and activating key PCa cell plasticity mechanisms including gene changes consistent with epithelial-to-mesenchymal transition (EMT) and a neuroendocrine phenotype. Additionally, analysis of publicly available clinical PCa tumor data showed metastatic prostate tumors demonstrate a positive correlation between insulin receptor expression and the EMT transcription factor FOXC2. The insulin receptor is not suitable to target clinically however, our data shows that actions of insulin in PCa cells may be suppressed by inhibiting downstream signaling molecules, PI3K and ERK1/2. This study identifies for the first time, a mechanism for insulin-driven cancer cell motility and supports the concept that targeting insulin signaling at the level of the PCa tumor may extend the therapeutic efficacy of ADT.

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Xenograft, Transgenic, and Knockout Models of Prostate Cancer

Cited by 5 publications

References 164 publications

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy–Part I

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy–Part I

Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research

Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2

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