Response to Androgens and Androgen Receptor Antagonists in the Presence of Cytokines in Prostate Cancer

Čulig, Zoran

doi:10.3390/cancers13122944

Cited by 9 publications

(8 citation statements)

References 39 publications

(39 reference statements)

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“…Neutralization of hypoxia‐regulated proteins (IL‐8 and VEGF) inhibits enzalutamide‐induced tumor growth. Culig 32 suggested that IL‐8 is inversely correlated with AR, and that IL‐8 might regulate the neuroendocrine phenotype in PCa. Our data supported that the IL‐8 secretion derived from the interaction between PCa cells and prostate fibroblasts induces not only the expression of AR‐V7, but also that of NSE.…”

Section: Discussionmentioning

confidence: 99%

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

et al. 2022

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Background: Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCa during androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration.Methods: We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48).Results: The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48.

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Section: Discussionmentioning

confidence: 99%

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

et al. 2022

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“…maintenance of cell activation and survival signals. AR is also activated by Jak/STAT signaling pathway through IL-6 and possibly other cytokines [53][54][55]. MAP kinase and cytokine signaling pathways also activates the nuclear factor "kappalight-chain-enhancer" of activated B-cells (NF-κB) pathway, which has been implicated in various cancers including prostate cancer.…”

Section: Pca and Androgen Signalingmentioning

confidence: 99%

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Varisli¹,

TOLAN²,

CEN³

et al. 2022

Oncology Research

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Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries. Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years. The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling. Although a partly remediation is accomplished at the beginning of treatment, some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching, from E-cadherin to Ncadherin, which is the hallmark of epithelial-mesenchymal transition. Diverse direct and indirect mechanisms are involved in this switching and consequently, the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells. Since E-cadherin represses invasive and migrative behaviors of the tumor cells, the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation. In this study, we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-β pathway.

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“…Moreover, activation of the androgen receptor by IL-6 in some subtypes of PC is associated with increased growth of tumor cells in vitro and in vivo . It has been reported that some molecules such as niclosamide and gallilactone can be very effective in simultaneously inhibiting the STAT3 pathway as well as the androgen receptor ( 44 ). The synergistic effect of TGF-β and epidermal growth factor (EGF) has also been shown to lead to the metastasis of tumor cells to the bone in PC.…”

Section: Involved Cytokines In the Pathogenesis Of Pcmentioning

confidence: 99%

A Double-Edged Sword Role of Cytokines in Prostate Cancer Immunotherapy

Mao

Ding

2021

Front. Oncol.

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Prostate cancer (PC) is one of the most common malignancies among men and is the second leading cause of cancer death. PC immunotherapy has taken relatively successful steps in recent years, and these treatments are still being developed and tested. Evidence suggests that immunotherapy using cytokines as essential mediators in the immune system may help treat cancer. It has been shown that cytokines play an important role in anti-tumor defense. On the other hand, other cytokines can also favor the tumor and suppress anti-tumor responses. Moreover, the dose of cytokine in cancer cytokine-based immunotherapy, as well as the side effects of high doses, can also affect the outcomes of treatment. Cytokines can also be determinative in the outcome of other immunotherapy methods used in PC. In this review, the role of cytokines in the pathogenesis of cancer and their impacts on the main types of immunotherapies in the treatment of PC are discussed.

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Response to Androgens and Androgen Receptor Antagonists in the Presence of Cytokines in Prostate Cancer

Cited by 9 publications

References 39 publications

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

A Double-Edged Sword Role of Cytokines in Prostate Cancer Immunotherapy

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