NR2F2 regulates bone marrow-derived mesenchymal stem cell-promoted proliferation of Reh cells

Zhu, Ni; Wang, Huafang; Wei, Jieping; Wang, Binsheng; Shan, Wei; Lai, Xiaoyu; Zhao, Yanmin; Yu, Jian; Huang, He

doi:10.3892/mmr.2016.5389

Cited by 12 publications

(12 citation statements)

References 19 publications

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“…BMSCs have been reported to induce tumor cell resistance by increasing VEGF secretion. 40,41 Additionally, vascular niche can regulate the survival and cell cycle of acute myeloid leukemia cells by secreting VEGF. 42 As a potent proangiogenic factor, cytokine VEGF functions by activating the VEGFR family, regulates vascular growth, and protects leukemia cells from apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Wang

Lü

et al. 2019

J of Cellular Biochemistry

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Chemoresistance often causes treatment failure of B‐cell acute lymphoblastic leukemia (B‐ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase‐1 (HO‐1) was found in the bone marrow stromal cells (BMSCs) from B‐ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B‐ALL cell lines Super B15 and CCRF‐SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO‐1. Silencing HO‐1 expression in BMSCs increased the apoptotic rates of B‐ALL cell lines induced by VCR, whereas upregulating HO‐1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B‐ALL cells were arrested in the G0/G1 phase due to HO‐1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment‐associated chemoresistance, was also positively coexpressed with HO‐1. VEGF secretion was markedly increased in BMSCs with HO‐1 upregulation but decreased in BMSCs with HO‐1 silencing. B‐ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO‐1 expression may promote the VCR resistance of B‐ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO‐1. In conclusion, this study clarifies a mechanism by which B‐ALL is induced to resist VCR through HO‐1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Wang

Lü

et al. 2019

J of Cellular Biochemistry

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“…According to several studies, it is evident that MSCs possess the ability to inhibit or promote tumor growth by suppressing proliferation or apoptosis of tumor cells, respectively, in hematologic malignancies [7, 10, 12]. Although minor reports have shown that MSCs can directly promote proliferation of hematologic malignant cells or promote apoptosis [20, 21], the primary hypothesis is that MSCs suppress both proliferation and apoptosis. Thus the use of MSCs for the treatment of hematologic malignancies is currently unclear, because inhibitory and promoting effects of MSCs on malignancies are known, both in vitro and in vivo [22, 23].…”

Section: Dual Role Of Mscs In Hematologic Malignancy Progression: Mscmentioning

confidence: 99%

Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges

et al. 2019

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Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Numerous studies have been conducted to adapt MSCs for further clinical use; however, the results have been inconclusive, possibly due to the heterogeneity of MSC populations. Moreover, the conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in hematologic malignancies are not as well established as they are for solid malignancies, and data comparing them are still limited. Herein the effect of MSCs on hematologic malignancies, such as leukemia and lymphoma, their mechanisms, sources of MSCs, and their effects on different types of cancer, have been discussed. This review describes how MSCs preserve both antitumorigenic and protumorigenic effects, as they tend to not only inhibit tumor growth by suppressing tumor cell proliferation but also promote tumor growth by suppressing tumor cell apoptosis. Thus clinical studies trying to adapt MSCs for anticancer therapies should consider that MSCs could actually promote hematologic cancer progression. It is necessary to take extreme care while developing MSC-based cell therapies in order to boost anticancer properties while eliminating tumor-favoring effects. This review emphasizes that research on the therapeutic applications of MSCs must consider that they exert both antitumorigenic and protumorigenic effects on hematologic malignancies.

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“…During the last years, MSCs-elicited effects on various types of cancer, including hematologic malignancies, their mechanisms, and also sources along with their advantages and disadvantages have been argued 26) . Several suggested mechanisms are citing the effects of MSCs in hematologic malignancies, but the most commonly believed mechanism is that MSCs could stimulate tumor cell cycle arrest [27][28][29] . Consequently, identifying MSCs' dual roles in leukemic cell proliferation and apoptosis is of paramount importance.…”

Section: Discussionmentioning

confidence: 99%

MSCs modifies the proliferation of leukemia MOLT-4 cells and induces their apoptosis through up-regulating Bax, caspase-3, and-8, and down-regulating Bcl-2 expression

Rahbaran

Baghini

Mardasi

et al. 2021

Ann. Cancer Res. Therap.

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Currently, it has been suggested that human mesenchymal stem cells (MSCs), a well-known multipotent stem cells, could modify the biological process in leukemia cells. Therefore, we evaluated human MSCs' possible effects on apoptosis and proliferation of acute lymphoblastic leukemia (ALL) MOLT-4 cells. Accordingly, MOLT-4 cells were co-cultured with MSCs. Then, 24, 48, and 72 hours after treatment, the apoptosis percentages of co-cultured MOLT-4 cell apoptosis was estimated using flow cytometry analysis. Also, cells proliferation rates were measured by MTT assay after 24, 48, and 72 hours of treatment. Finally, the expression ratio of candidate genes, including Bax, Bcl-2, and caspase-3, and -8, were evaluated in MOLT-4 cells co-cultured with MSCs. Based on results, MSCs stimulated the apoptosis of MOLT-4 cells after 48 and 72 hours but not 24 hours of treatment compared with the control group (MOLT-4 cells). Also, MSCs induced robust a reduction in MOLT-4 cell proliferation rate compared with the control group. On the other hand, Real-Time PCR results indicated a decrease in Bcl-2 expression, and conversely a promotion in Bax, and caspase-3, and -8 expression at mRNA levels. In sum, results signified that MSCs could exert anti-leukemic effects on leukemia MOLT-4 cells through promoting Bax/Bcl-2 ration concomitant with up-regulating caspases expression.

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NR2F2 regulates bone marrow-derived mesenchymal stem cell-promoted proliferation of Reh cells

Cited by 12 publications

References 19 publications

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges

MSCs modifies the proliferation of leukemia MOLT-4 cells and induces their apoptosis through up-regulating Bax, caspase-3, and-8, and down-regulating Bcl-2 expression

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