G allele of rs7853346 polymorphism in PTENP1 enhances the proliferation of multiple myeloma cancer stem cells by promoting the expression of PTENP1 and its downstream signaling molecules

2019 ◽  
Vol 120 (12) ◽  
pp. 19738-19748 ◽  
Author(s):  
Yehua Zhang ◽  
Changqing Xu
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells ◽  
Signaling Molecules ◽  
Downstream Signaling

scholarly journals Differential Expression of MicroRNA-19b Promotes Proliferation of Cancer Stem Cells by Regulating the TSC1/mTOR Signaling Pathway in Multiple Myeloma

2018 ◽  
Vol 50 (5) ◽  
pp. 1804-1814 ◽  
Author(s):  
Ni Wang ◽  
Xiaohua Liang ◽  
Weijian Yu ◽  
Shihang Zhou ◽  
Meiyun  Fang
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells ◽  
Real Time ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Luciferase Assay ◽  
Downstream Target ◽  
Induced Apoptosis

Background/Aims: MiR-19b has been reported to be involved in several malignancies, but its role in multiple myeloma (MM) is still unknown. The objective of this study was to explore the biological mechanism of miR-19b in the progression of MM. Methods: First, we performed real-time polymerase chain reaction (PCR) and Western blot to study the expression of miR-19b, tuberous sclerosis 1 (TSC1), and caspase-3 in different groups. MTT assay was performed to explore the effect of miR-19b on survival and apoptosis of cancer stem cells (CSCs). Computation analysis and luciferase assay were utilized to confirm the interaction between miR-19b and TSC1. Results: A total of 38 participants comprising 20 subjects with MM and 18 healthy subjects as normal controls were enrolled in our study. Real-time PCR showed dramatic upregulation of miR-19b, but TSC1 was evidently suppressed in the MM group. MiR-19b overexpression substantially promoted clonogenicity and cell viability, and further inhibited apoptosis of CSCs in vitro. Furthermore, miR-19b overexpression downregulated the expression of caspase-3, which induced apoptosis. Using in silico analysis, we identified that TSC1 might be a direct downstream target of miR-19b, and this was further confirmed by luciferase assay showing that miR-19b apparently reduced the luciferase activity of wild-type TSC1 3´-UTR, but not that of mutant TSC1 3´-UTR. There was also evident decrease in TSC1 mRNA and protein in CSCs following introduction of miR-19b. Interestingly, reintroduction of TSC1 abolished the miR-19b-induced proliferation promotion and apoptosis inhibition in CSCs. Conclusion: These findings collectively suggest that miR-19b promotes cell survival and suppresses apoptosis of MM CSCs via targeting TSC1 directly, indicating that miR-19b may serve as a potential and novel therapeutic target of MM based on miRNA expression.

scholarly journals PEGylated long-circulating liposomes deliver homoharringtonine to suppress multiple myeloma cancer stem cells

2017 ◽  
Vol 242 (9) ◽  
pp. 996-1004 ◽  
Author(s):  
Miao Li ◽  
Fangfang Shi ◽  
Xiong Fei ◽  
Songyan Wu ◽  
Di Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells

scholarly journals A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 655 ◽  
Author(s):  
Christian Kaltschmidt ◽  
Constanze Banz-Jansen ◽  
Tahar Benhidjeb ◽  
Morris Beshay ◽  
Christine Förster ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
The Status ◽  
Organ Specific ◽  
Proliferation And Metastasis ◽  
Cancer Multiple

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

The TGF- β Family Member Growth Differentiation Factor 15 (GDF15) Regulates the Self-Renewal of Multiple Myeloma Cancer Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2954-2954
Author(s):  
Toshihiko Tanno ◽  
Akil Merchant ◽  
Jasmin R. Agarwal ◽  
Qiuju Wang ◽  
William Matsui
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cancer Stem Cells ◽  
The Self ◽  
Disease Stage ◽  
Dependent Manner ◽  
Self Renewal ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Abstract Abstract 2954 Multiple myeloma (MM) cancer stem cells (CSCs) possess both enhanced tumorigenic potential and relative drug resistance suggesting they play a major role in disease relapse and progression. Therefore, a better understanding of the processes regulating MM CSCs may lead to the development of novel therapies that prevent tumor regrowth and improve long-term outcomes. Normal stem cells are tightly regulated by factors within the local microenvironment that include both soluble factors and direct contact with accessory cells. However, external factors regulating MM CSCs have not been identified. Recent studies have demonstrated that stromal cells in the MM bone marrow microenvironment secrete growth differentiation factor 15 (GDF15), a member of the TGF-b family. We initially studied the role of this cytokine in the pathogenesis of MM by examining circulating GDF15 levels in MM patients. Compared to healthy volunteers, we found that median GDF15 levels were significantly increased in MM patients (821 vs. 390 pg/ml; n=16; p<0.05) and increased with disease stage (Stage II=585 pg/ml, Stage III=1, 004 pg/ml). To examine the functional effects of GDF15 on MM cells, we cultured human MM cell lines (NCI-H929, RPMI 8226) with recombinant GDF15 and found that it induced the expansion of isolated CD138neg MM CSCs in a dose-dependent manner but had little impact on the growth of CD138+ plasma cells (Fig). Furthermore, GDF15 enhanced clonogenic myeloma growth as evidenced by increased colony formation that was maintained during serial replating, a surrogate for self-renewal. This effect appeared to be GDF15 specific since it could be blocked using anti-GDF15 antibody. Similarly, GDF15 treatment increased the in vitro clonogenic growth of MM CSCs from primary clinical bone marrow specimens. We also investigated the down-stream cellular pathways potentially mediating the effects of GDF15 and found that it activates the AKT signaling pathway known to improve the self-renewal of embryonic (ES) and normal hematopoietic stem cells. GDF15 also induced expression of the SOX2 transcription factor known to be upregulated in CD138neg MM CSCs. Since SOX2 is required for the self-renewal of ES cells and the generation of induced pluripotent stem (iPS) cells, its induction by GDF15 may also increase the self-renewal of MM CSCs. GDF15 is the first soluble factor identified that regulates MM CSCs, and its effects are mediated by the activation of highly conserved self-renewal programs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

Oncotarget ◽  
2015 ◽  
Vol 6 (38) ◽  
pp. 40496-40506 ◽  
Author(s):  
Reinaldo Franqui-Machin ◽  
Erik B. Wendlandt ◽  
Siegfried Janz ◽  
Fenghuang Zhan ◽  
Guido Tricot
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Drug Resistance ◽  
Cancer Stem Cells

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

2013 ◽  
Vol 13 (1) ◽  
pp. 144-153 ◽  
Author(s):  
A. Morgenroth ◽  
A. T. J. Vogg ◽  
B. D. Zlatopolskiy ◽  
M. Siluschek ◽  
C. Oedekoven ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells ◽  
Cell Subpopulation

scholarly journals Cancer stem cells: controversies in multiple myeloma

2009 ◽  
Vol 87 (11) ◽  
pp. 1079-1085 ◽  
Author(s):  
Sarah K. Brennan ◽  
William Matsui
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells

B206 Characterization of Cancer Stem Cells in Multiple Myeloma

2009 ◽  
Vol 9 ◽  
pp. S112
Author(s):  
E Sanchez ◽  
JR Berenson ◽  
H Chen ◽  
M Li ◽  
CS Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells

scholarly journals Targeting Multiple Myeloma Cancer Stem Cells with Natural Products – Lessons from Other Hematological Malignancies

Planta Medica ◽  
2017 ◽  
Vol 83 (09) ◽  
pp. 752-760 ◽  
Author(s):  
Mark Issa ◽  
Sylvian Cretton ◽  
Muriel Cuendet
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Hematological Malignancies ◽  
Plasma Cells ◽  
Chemical Structures ◽  
Recent Advances ◽  
Promising Therapeutic Approach

AbstractMultiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Multiple myeloma is the second most frequently diagnosed hematological malignancy, predominantly affecting the elderly. Despite recent advances in the development of novel therapies, multiple myeloma remains an incurable malignancy where the majority of patients relapse, develop resistance, and eventually die from the disease. This has been attributed to the fact that conventional therapy currently in use targets mainly the bulk of tumor cells, but not the tumor-initiating cancer stem cells. Cancer stem cells are a highly resistant subpopulation of cells believed to be responsible for the initiation, progression, metastasis, and relapse of cancer. Enormous efforts have been invested in the characterization of cancer stem cells. These efforts led to the characterization of key cellular signaling pathways responsible for conferring stem cell characteristics including self-renewal, differentiation, migratory, survival, and intracellular detoxification capabilities. Targeting these protective mechanisms offers a valuable strategy that may help combat a major driving force behind cancers. The use of natural products offers a promising therapeutic approach for targeting cancer stem cells. In this review, recent advances achieved in the characterization of cancer stem cells derived from hematological malignancies, with a particular focus on multiple myeloma, are discussed and major natural products that target cancer stem cells are presented. As natural products remain an essential source of novel chemical structures and medicinal leads, the exploitation of this immense reservoir is used to draw lessons in targeting multiple myeloma-cancer stem cells.

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