SDF-1α inhibits hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells through PI3K/Akt and ERK1/2 signaling pathways

Yin, Qiushi; Jin, Peifeng; Liu, Xuebin; Hua, Wei; Liu, Xiaoming; Chi, Chuang; Liu, Yu; Sun, Chengcao; Wei, Yingjie

doi:10.1007/s11033-010-0071-9

Cited by 41 publications

(24 citation statements)

References 32 publications

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“…A recent report shows that SDF-1a-mediated PI3K/AKT and ERK1/1 signaling can prevent hypoxia-induced apoptosis in bone marrow-derived mesenchymal stem cells. 52 Whether similar mechanisms can occur in this tumor model requires further investigation, although we have found that the monocytic cell line, Raw264.7, in ALTS1C1 CM was more resistant to hypoxic stress than in SDF kd CM. As reported, 10,53 various subtypes of TAMs have different effects on tumor growth and prognosis.…”

Section: Sdf-1 Promotes Glioma Invasion and Tam Tropism S-c Wang Et Almentioning

confidence: 86%

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

Wang

Hong

Hsueh

et al. 2012

Laboratory Investigation

157

143

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A distinguishing feature of high-grade gliomas is the infiltration of neoplastic cells into adjacent brain tissues that mark most of these tumors surgically incurable. To study the factors associated with tumor invasion, we established a new murine brain tumor model, ALTS1C1 derived from SV40 large T antigen-transfected astrocytes. This new brain tumor model recapitulates several histopathological features of human high-grade glioma including increased cellularity, prominent cellular pleomorphism, geographic necrosis, active mitosis, and extensive invasion of tumor cells into adjacent brain tissues. More importantly, ALTS1C1 expressed a relatively high level of stromal-derived factor-1 (SDF-1/CXCL12) in vitro and in vivo and higher microvascular density (MVD) in vivo. To define the roles of SDF-1 in this tumor model, the expression of SDF-1 in ALTS1C1 cells was inhibited by specific siRNA. SDF-knockdown ALTS1C1 (SDF kd ) cells took longer than parental ALTS1C1 cells to form tumors and in contrast to the wild-type tumors they had well-defined regular borders and lacked infiltration tracts. The SDF kd tumors were also associated with a lower MVD and more hypoxic areas. In contrast to parental tumors, the density of F4/80-positive tumor-associated macrophages (TAMs) in SDF kd tumor was higher in non-hypoxic than in hypoxic regions. SDF-1 production by tumor cells therefore seems critical for the aggregation of TAMs into areas of hypoxia and tumor invasiveness. This study not only provides new insight into the role of SDF-1 in brain tumor invasion and the relationship between TAMs and hypoxia, but also provides a new preclinical brain tumor model for designing new treatment options for invasive cases.

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Section: Sdf-1 Promotes Glioma Invasion and Tam Tropism S-c Wang Et Almentioning

confidence: 86%

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

Wang

Hong

Hsueh

et al. 2012

Laboratory Investigation

157

143

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“…Yin et al showed that addition of 0.5-2 mg/ml of SDF-1 inhibited hypoxia and serum deprivation-induced apoptosis of MSCs. 66 The effect was abolished by PI3K inhibitor wortmannin, indicating the important role of the PI3K/Akt pathway in SDF-1-increased MSC survival.…”

Section: The Pi3k/akt Pathway and Survival Ability Of Mscsmentioning

confidence: 93%

“…Stromal cell-derived factor-1 (SDF-1) has been shown to increase MSC survival by several studies. [66][67][68] Liu et al demonstrated that SDF-1 can increase the resistance of MSCs to apoptosis induced by H 2 O 2 . 39 The pretreatment of MSCs with SDF-1 significantly reduced apoptosis by activating the PI3K/Akt pathway.…”

Section: The Pi3k/akt Pathway and Survival Ability Of Mscsmentioning

confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

205

161

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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“…26,27 Many studies have shown that some clinical chemotherapeutic agents could induce cancer cell apoptosis via regulating MAPKs and Akt kinase activity. [28][29][30] To determine the role of these kinases in tetrandrine-induced HCC apoptosis, Western blot analysis was used to evaluate the activity of MAPKs and Akt-related proteins after tetrandrine treatment. Cancer Therapy The results showed that phosphorylated levels of ERK1/2, JNK and Akt decreased after tetrandrine treatment, but there was no significant change in phospho-p38 protein level (Fig.…”

Section: Tetrandrine Induces Hcc Cell Apoptosis Through Inhibition Ofmentioning

confidence: 99%

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Liu¹,

Gong²,

Mao³

et al. 2011

Intl Journal of Cancer

130

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Tetrandrine, a bisbenzylisoquinoline alkaloid component of broadly used traditional Chinese medicine, has antitumor effects against some cancers. In our study, we investigated the effects of tetrandrine on the human hepatocellular carcinoma (HCC) in vitro and in vivo. The results showed that tetrandrine effectively induced apoptosis of liver cancer cell in a dose-and time-dependent manner accompanied by alteration of cell morphology, chromatin fragmentation and caspase activation. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS), and ROS scavengers (LNAC and GSH) completely blocked the effects of tetrandrine-induced apoptosis, suggesting that the generation of ROS plays an important role in tetrandrine-induced apoptosis. Although the activities of JNK and ERK were inhibited significantly by tetrandrine treatment, JNK and ERK are not involved in the tetrandrine-induced apoptosis. In contrast, Akt activity was found to be closely related to tetrandrine-induced apoptosis. The data demonstrated that Akt activity inhibitor LY294002 synergistically promoted tetrandrine-induced apoptosis of HCC, whereas ectopic expression of Akt contrastly abrogated partial of the tetrandrine-induced apoptosis. These data suggest that Akt signal is the downstream event of ROS generation in the tetrandrine-induced HCC cell apoptosis. Moreover, the results of xenograft in nude mice were consistent with that of the in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of HCC as a regulator of ROS/Akt pathway.

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SDF-1α inhibits hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells through PI3K/Akt and ERK1/2 signaling pathways

Cited by 41 publications

References 32 publications

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

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