Natural killer cells suppress enzalutamide resistance and cell invasion in the castration resistant prostate cancer via targeting the androgen receptor splicing variant 7 (ARv7)

Lin, Shin-Jen; Chou, Fu-Ju; Li, Lei; Lin, Chien-Chou; Yeh, Shuyuan; Chang, Chawnshang

doi:10.1016/j.canlet.2017.03.035

Cited by 33 publications

(24 citation statements)

References 38 publications

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“…Previous study has documented that NK cells could suppress AR expression (17). Consistently, we also found that the protein levels of AR in both CWR22Rv1 ( Fig.…”

Section: Ar Renders Lp-mediated Nk Cytotoxicity To Pca Cellssupporting

confidence: 91%

Leinal polypeptide promotes NK cells to suppress PCa survival inï¿½vitro

Rao

Zhang

et al. 2018

Oncol Lett

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As an important component in the innate immune system, natural killer (NK) cells have been demonstrated to be clinically associated with prostate cancer (PCa) progression and castration resistance. Therefore, the development of novel agents that may enhance the cytotoxicity of NK cells possesses promising therapeutic applications. In the present study, leinal polypeptide (LP) solution was supplemented into a co-culture system of NK and PCa cells, as it was previously demonstrated that LP are able to activate NK cells, which kill PCa cells based on an MTT cell viability assay. Mechanistic dissection demonstrated that LP enhanced androgen receptor degradation, which resulted in an upregulation of MHC class I polypeptide-related sequence A (MICA) and MICB. In turn, the induced expression of MICA and MICB was able to further trigger NK cell activation, forming a positive loop between NK cells and PCa cells in the presence of LP solution.

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“…Previous study has documented that NK cells could suppress AR expression (17). Consistently, we also found that the protein levels of AR in both CWR22Rv1 ( Fig.…”

Section: Ar Renders Lp-mediated Nk Cytotoxicity To Pca Cellssupporting

confidence: 91%

Leinal polypeptide promotes NK cells to suppress PCa survival inï¿½vitro

Rao

Zhang

et al. 2018

Oncol Lett

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“…In addition, various immune cells in the tumor microenvironment influence the progression of HCC [3,19]. AR alters NK cells cytotoxicity by suppressing Interleukin (IL)-12A expression in HCC cells, revealing a relationship between the cytotoxicity of NK cells and AR in HCC [13,33]. Thus, the potential connection between AR and immune surveillance during HCC progression merits further evaluation.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression

et al. 2020

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Background: Androgen receptor (AR) has a role in regulating malignancies and gender disparities in hepatocellular carcinoma (HCC). Recently, TLR4 activation is demonstrated to be required for HCC progression; however, whether and how TLR4 interacts with AR is largely unknown. Methods: The tumorigenesis was detected in female and male mice induced by DEN/CCL4, then TLR4 and AR signals were detected in liver tissues by qPCR and FACS. The proliferation, colony formation and migration of HCC cell treated with TLR4 agonist LPS, or/and androgen DHT were evaluated in vitro. Furthermore, the expression of TLR4 and AR was detected by IHC in tissue microarray of HCC, and correlation of AR and TLR4 was defined. Results: Male mice are more susceptible to develop HCC than female mice. Meanwhile, we found baseline TLR4 levels were higher in male mice than in female mice. AR expression in male mice was increased by treatment with DEN/CCL4. And, AR was constitutively expressed in human HCC cell lines. Dihydrotestosterone (DHT) stimulated TLR4 expression in both HepG2 and HepG2 2.15 cells, which could be blocked by silencing AR. On the other hand, treatment with LPS stimulated AR expression, but it was blocked by treatment with TLR4 antagonist and in cells deficient for TLR4. DHT treatment exacerbated TLR4-induced cellular proliferation, colony formation, migration, and invasion of HepG2 cells. The positive relationship between AR and TLR4 was confirmed in human HCC samples. Conclusions: DHT-AR-TLR4 signaling enhances the development of HCC cells and facilitates their migration and invasion, demonstrating a mechanism underlying gender disparity in HCC.

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“…Thus, the role of NK cells in suppressing the progression of various tumors is becoming increasingly apparent (20,21). Their roles in patients with metastatic PC have also been extensively evaluated (22,23). However, only two studies to date have investigated the efficacy of NKA as a screening tool for PC, with conflicting results (14,15).…”

Section: Discussionmentioning

confidence: 99%

Can natural killer cell activity help screen patients requiring a biopsy for the diagnosis of prostate cancer?

et al. 2020

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Purpose: To evaluate the usefulness of natural killer cell activity (NKA) in diagnosing prostate cancer (PC). Materials and Methods: The medical records of patients who underwent transrectal prostate biopsy (TRBx) at Korea University Ansan Hospital between May 2017 and December 2017 were retrospectively reviewed. NKA levels were measured using NK Vue® Tubes (ATgen, Sungnam, Korea). All blood samples were obtained at 8 AM on the day of biopsy. Patients with other malignancies, chronic infl ammatory conditions, high prostate-specifi c antigen (PSA) level (>20ng/mL), or history of taking 5-alphareductase inhibitor or testosterone replacement therapy were excluded. Results: A total of 102 patients who underwent TRBx for PC diagnosis were enrolled. Among them, 50 were diagnosed with PC. Signifi cant differences in age and NKA level were observed between the PC and no-PC groups. Receiver operating characteristic (ROC) curve analysis showed that the optimal cutoff of NKA level for the prediction of PC was 500pg/dL, with a sensitivity of 68.0% and a specifi city of 73.1%. In addition, NKA level (0.630) had the greatest area under the ROC curve compared to those for the ratio of total PSA to free PSA (0.597) and PSA density (0.578). Conclusions: The results of this pilot study revealed that low NKA and high PSA levels were likely to be associated with a positive TRBx outcome. NKA detection was easy and improved the diagnostic accuracy of PC.

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Natural killer cells suppress enzalutamide resistance and cell invasion in the castration resistant prostate cancer via targeting the androgen receptor splicing variant 7 (ARv7)

Cited by 33 publications

References 38 publications

Leinal polypeptide promotes NK cells to suppress PCa survival inï¿½vitro

Leinal polypeptide promotes NK cells to suppress PCa survival inï¿½vitro

Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression

Can natural killer cell activity help screen patients requiring a biopsy for the diagnosis of prostate cancer?

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