Bone Marrow Stromal Cells Promotes Morphological Senescence of Prostate Cancer Cells and Inhibits Metastasis Associated 1 Gene Level

2022 ◽  
Vol 12 (4) ◽  
pp. 711-716
Author(s):  
Xuechuan Yan ◽  
Xin Wang ◽  
Haifeng Yang ◽  
Jian Yang ◽  
Haikun Li
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Inhibitory Effect ◽  
Cell Number ◽  
Cell Senescence ◽  
Marrow Stromal Cells ◽  
Cancer Group ◽  
Gene Level

This study assessed the mechanism of Bone Marrow Stromal Cells (BMSCs) in prostate cancer (PC) and its effect on MTA-1 gene and PC cell senescence. PC-3 cells were assigned into QL group (prostate cancer group: normal culture) and GS group (BMSCs group: treated with BMSCs) followed by analysis of MTA-1 level, cell senescence, apoptosis and invasion. MTA-1 level in QL group (0.83±0.07) was significantly higher than GS group (0.14±0.02) (P < 0.05), indicating that BMSCs had an inhibitory effect on MTA-1 expression. Similar change of MTA-l mRNA was also found with higher level in QL group than GS group (P < 0.05). Cell senescence was found in QS group but not QL group, indicating that BMSCs promote cell senescence. Compared with GS group, QL group has a higher cell number in G0/G1 (67.13±6.45%) and S (19.59±3.35%) than GS group (G0/G1:50.51±2.19% and S: 11.42±1.61%) but lower G2/M (QL: 15.97±3.59% versus GS: 32.25±3.24%). QL group had significantly lower cell apoptosis rate at 35 h (5.21±1.2%) and 45 h (3.97±0.95%) than GS group at 35 h (17.85±1.23%), 45 h (10.21±1.26%) with elevated number of invasions. In conclusion, BMSCs promote PC-3 cell senescence and apoptosis by inhibiting the expression of MTA-1 and reduce cell invasion ability.

scholarly journals Long non‐coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chuan-yi Hu ◽  
Juan Chen ◽  
Xin-hua Qin ◽  
Pan You ◽  
Jie Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Downstream Target ◽  
Non Coding Rna ◽  
Target Molecules ◽  
Long Non Coding Rna

Abstract Background Bone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa. Methods NORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD. Results PCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells. Conclusions NORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.

Bone marrow stromal cells promote growth and survival of prostate cancer cells

2007 ◽  
Vol 35 (4) ◽  
pp. 698-700 ◽  
Author(s):  
N.A. Cross ◽  
M. Papageorgiou ◽  
C.L. Eaton
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Cancer Cell Proliferation ◽  
Growth And Survival ◽  
Prostate Cancers ◽  
Necrosis Factor ◽  
Insulin Like Growth Factors

Prostate cancers frequently metastasize to the skeleton, and it has been hypothesized that this environment selectively supports the growth of these tumours. Specifically there is strong evidence that interactions between tumour cells and BMSCs (bone marrow stromal cells) play a major role in supporting prostate cancer growth and survival in bone. Here, we examine factors shown to be secreted by BMSCs, such as IGFs (insulin-like growth factors) and IL-6 (interleukin 6), shown to promote prostate cancer cell proliferation and to potentially replace the requirement for androgens. In addition we discuss another factor produced by BMSCs, osteoprotegerin, which may promote tumour cell survival by suppressing the biological activity of the pro-apoptotic ligand TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand).

Bone Marrow Stromal Cells Reverse Proapoptotic Effects of JAK2 Inhibitor Atiprimod in Cells Carrying the JAK2V617F mutation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3738-3738
Author(s):  
Taghi Manshouri ◽  
Zeev Estrov ◽  
Jan Burger ◽  
Ana Livun ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Inhibitory Effect ◽  
Marrow Stromal Cells ◽  
Stat Proteins ◽  
Jak2 Inhibitor ◽  
Growth Inhibitory ◽  
Induced Apoptosis ◽  
Mutant Cells

Abstract Janus kinases (JAK) comprise a small family of cytoplasmic protein tyrosine kinases, which play an important role in the initiation of cytokine-triggered signaling events via signal transducer and activator of transcription (STAT) proteins. The recent reports of an activating somatic mutation in codon 617 of the JAK2 gene (JAK2V617F mutation) in patients with myeloproliferative disorders (MPDs), has opened new avenues for the development of targeted therapies for these malignancies and clinical trials with JAK2 inhibitors are underway. We report here the activity of Atiprimod (N,N-diethyl-8-dipropyl-2-azaspiro[4,5]decane-2-propanamine), a novel compound with anti-inflammatory properties, in retrovirus-transduced JAK2V617F mutant-expressing murine FDCP-EpoR cells, set-2 cells, and blood cells from patients with polycythemia vera (PV). We compared the growth inhibitory effect of Atiprimod against two mouse FDCP cell lines transfected with erythropoietin receptor (Epo-R), and either wild-type JAK2WT or mutant JAK2V617F, and human megakaryoblastic leukemia cells with mutated JAK2V617F (set-2 cells). The growth inhibitory effect was assessed using 3-days MTS assay. Atiprimod was more potent against FDCP cells carrying mutant JAK2V617F cells (IC50 0.42 μM) and set-2 cells (IC50 0.53 μM) than FDCP wildtype JAK2WT cells (IC50 0.69 μM). Atiprimod inhibited the phosphorylation of JAK2 and downstream STAT3, STAT5, and AKT proteins in a dose- and time-dependent manner. It induced apoptosis, as evidenced by increase in mitochondrial membrane potential, caspase3 activity, and cleavage of PARP protein. The anti-proliferative effect on expanded PV patient progenitor’s cells was paralleled by a decrease in JAK2V617F mutant allele frequency in BFU-E or CFU-GM clones in clonogenic assay. However, co-culturing of JAK2V617F mutant cells with three different bone marrow stromal cell lines (Hs5, ABM-MSC, NK-Tert) either directly (cell on cell) or indirectly (separated by 0.4 μm micropore membranes) for 48 hours resulted in a significant protection of mutant cells from the effect of Atiprimod. Co-culturing of bone marrow stromal cells prevented Atiprimod (0.4 and 0.8 μM) induced apoptosis, and reversed the inhibition of phosphorylation of STAT proteins. Our results suggest that cytokines secreted by stromal cells might play an important role in protecting the hematopoietic cells from a JAK2 inhibitor. Further dissection of the nature of interactions between JAK2V617F mutant cells and marrow stromal cells may lead to new therapeutic avenues for patients with MPD.

Human Bone Marrow Stromal Cells Protect Prostate Cancer Cells From TRAIL-Induced Apoptosis

2004 ◽  
Vol 19 (10) ◽  
pp. 1712-1721 ◽  
Author(s):  
Rachel Nyambo ◽  
Neil Cross ◽  
Jenny Lippitt ◽  
Ingunn Holen ◽  
Gorden Bryden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Prostate Cancer Cells ◽  
Induced Apoptosis
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