Transforming growth factor‐β signaling induced during prostate cancer cell death and neuroendocrine differentiation is mediated by bone marrow stromal cells

Miles, Fayth L.; Kurtoglu, Senem; Ahmer, Chris; Soori, Mehrnoosh; Favate, John; Sikes, Robert A.

doi:10.1002/pros.23060

Cited by 6 publications

(12 citation statements)

References 33 publications

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“…After that, cells were cultured in DMEM/F12 medium (Hyclone Co, USA) containing mineralization induction agents (0.05 g/L vitamin C, 40 ng/mL dexamethasone and 10 mmol/L β-sodium glycerol phosphate) and 10% fetal bovine serum at 37°C with 5% CO 2 . After two weeks of induced culturing, according to our previous study [ 18 ], cells were seeded into a 96-well plate at a density of 1×10 4 cells per well, and then were treated with fluoride at concentrations of 1 mg/L, 4 mg/L and 16 mg/L with or without 10 μmol/L SB431542 as previously described [ 19 ]. Control group was cultured in medium without fluoride and SB431542.…”

Section: Methodsmentioning

confidence: 99%

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Yang

Wang

2017

PLoS ONE

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This study aimed to preliminary investigate the role of activin receptor-like kinase (ALK) 5 as one of TGF-βR1 subtypes in bone turnover and osteoblastic differentiation induced by fluoride. We analyzed bone mineral density and the expression of genes related with transforming growth factor-β1(TGF-β1) signaling and bone turnover in rats treated by different concentrations of fluoride with or without SB431542 in vivo. Moreover, MTT assay, alkaline phosphatase staining, RT-PCR, immunocytochemical analysis and western blot analysis were used to detect the influence on bone marrow stem cells (BMSC) after stimulating by varying concentration of fluoride with or without SB431542 in vitro. The in vivo study showed SB431542 treatment affected bone density and gene expression of rats, which indicated TGF-β1 and ALK5 might take part in fluoride-induced bone turnover and bone formation. The in vitro study showed low concentration of fluoride improved BMSC cells viability, alkaline phosphatase activity, and osteocalcin protein expression which were inhibited by high concentration of fluoride. The gene expression of Runx2 and ALK5 in cells increased after low concentration fluoride treatment which was also inhibited by high concentration of fluoride. Fluoride treatment inhibited gene and protein expression of Samd3 (except 1 mgF-/L). Compared with fluoride treatment alone, cells differentiation was inhibited with SB431542 treatment. Moreover, the expression of Runx2, ALK5 and Smad3 were influenced by SB431542 treatment. In conclusion, this preliminary study indicated that fluoride regulated osteoblastic TGFβ1 signaling in bone turnover and cells differentiation via ALK5.

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Section: Methodsmentioning

confidence: 99%

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Yang

Wang

2017

PLoS ONE

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“…In PCa, bone is one of the preferred sites for metastasis for adenocarcinoma. During bone metastasis, the cross-talk between PCa cells and BMSCs plays a crucial role in cell survival and apoptosis [29,178]. It has been reported that TGF-β secreted from BMSCs induces pronounced apoptosis in the androgen-dependent cells (LNCaP) compared to androgen independent (C4-2) cells.…”

Section: Neuroendocrine Trans-differentiation (Ned)mentioning

confidence: 99%

“…It has been reported that TGF-β secreted from BMSCs induces pronounced apoptosis in the androgen-dependent cells (LNCaP) compared to androgen independent (C4-2) cells. TGF-β signaling in PCa cells leads to NE differentiation [29]. Although primary NEPC rarely metastasize to the bone, in t-NEPC up to 15% of the bone metastasis are NEPC [20].…”

Section: Neuroendocrine Trans-differentiation (Ned)mentioning

confidence: 99%

“…In addition, recent progress has led to a widespread appreciation of the reciprocal communications between PCa cells and the cells of the tumor microenvironment (TME), e.g., mast cells, macrophages, bone marrow stromal cells (BMSCs), and cancer associated fibroblasts (CAFs), and how these interactions are critical in shaping PCa progression including NED [24,25,26,27,28,29,30]. The primary factors that make NEPC the most lethal form of PCa is due to the lack of response of the AR to ADT, in part due to weak or absent AR and prostate-specific antigen (PSA); thereby, presenting a therapeutic challenge in the clinic.…”

Section: Introductionmentioning

confidence: 99%

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Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

Patel

Chugh

Tripathi

2019

Cancers

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Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.

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“…TGF‐β1 is a member of the TGF‐β superfamily. It is a multifunctional cytokine expressed in a variety of tissue cells, especially the liver (Li, Dong, Cao, & Chang, ; Miles et al, ; Wang, Song, Liu, Fang, & Xiao, ; Wincewicz et al, ). TGF‐β1 participates in various pathophysiological processes of mammals extensively and affects cell proliferation, differentiation, migration, apoptosis and other biological activities (Kajdaniuk, Marek, Borgiel‐Marek, & Kos‐Kudla, ).…”

Section: Introductionmentioning

confidence: 99%

TGF‐β1 elevates P‐gp and BCRP in hepatocellular carcinoma through HOTAIR/miR‐145 axis

Kong

Qiu

et al. 2019

Biopharm & Drug Disp

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Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor‐β1 (TGF‐β1) and overexpression of drug efflux transporters P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP), although the molecular mechanisms remain largely unknown. This study aimed to investigate the mechanisms underlying TGF‐β1‐induced MDR in hepatocellular carcinoma (HCC) cells. It was found that TGF‐β1 upregulated HOX transcript antisense RNA (HOTAIR) expression in HCC cells. When drosophila mothers against decapentaplegic 4 (SMAD4) was silenced, HOTAIR expression was accordingly reduced. Meanwhile, miR‐145 expression was increased in the case HOTAIR was silenced. If the enhancer of zeste homolog 2 (EZH2) was knocked down using small interfering RNA (siRNA), miR‐145 expression was decreased. Then, the regulatory role of miR‐145 in P‐gp and BCRP expression was explored. The results showed that the expression of P‐gp and BCRP protein was suppressed by miR‐145 through binding to the 3′‐untranslated regions (3′‐UTRs) of P‐gp and BCRP. In conclusion, our study revealed a novel mechanism explaining TGF‐β1‐induced MDR in HCC through upregulating P‐gp and BCRP via the SMAD4/HOTAIR/miR‐145 axis.

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Transforming growth factor‐β signaling induced during prostate cancer cell death and neuroendocrine differentiation is mediated by bone marrow stromal cells

Abstract: TGF-β signaling resulting in activation of SMAD2 in prostate cancer may be an indicator of cellular stress in the presence of toxic paracrine factors released from the bone marrow stroma, ultimately fostering prostate cancer colonization of bone.

Cited by 6 publications

References 33 publications

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

TGF‐β1 elevates P‐gp and BCRP in hepatocellular carcinoma through HOTAIR/miR‐145 axis

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