Mesenchymal stem cells generate pericytes to promote tumor recurrence via vasculogenesis after stereotactic body radiation therapy

Wang, Huan Huan; Cui, Yunlong; Zaorsky, Nicholas G.; Lan, Jie; Deng, Lei; Zeng, Xian; Wu, Zhaojun; Tao, Zhen; Guo, Wen; Wang, Qing Xin; Zhao, Lu; Yuan, Zhi Yong; Lü, You; Wang, Ping; Mao, Meng

doi:10.1016/j.canlet.2016.02.033

Cited by 72 publications

(47 citation statements)

References 56 publications

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“…Myofibroblasts, which may be present in prostate cancer, can also be educated by cytokines from cancer cells to be protumorigenic, similar to CAFs [142]. Pericytes, cells with properties similar to MSCs, are able to support tumor progression and chemotherapy survival after contact with cancer cells [83, 143, 144]. …”

Section: Comparison Between the Tumor Microenvironment And The Stementioning

confidence: 99%

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Aponte

Caicedo²

2017

Stem Cells International

308

187

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Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

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Section: Comparison Between the Tumor Microenvironment And The Stementioning

confidence: 99%

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Aponte

Caicedo²

2017

Stem Cells International

308

187

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“…Although general consensus and support for combination therapy exists, most standard cancer therapies have not been evaluated for their effects on the immune system, or those effects have been equivocal. For example, radiation releases tumor antigens (39), but also stimulates radiation-resistant mesenchymal stem cells which can cause local immunosuppression and make irradiated bone marrow a preferred metastatic niche (43). Chemotherapies kill rapidly dividing cells, with certain agents preferentially eliminating Tregs (44), MDSCs (45, 46), or even proliferating CD8 T cells (47).…”

Section: Introductionmentioning

confidence: 99%

Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy

Tyler

Servos

Vries

et al. 2017

Molecular Cancer Therapeutics

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Selinexor (KPT-330) is a first in class nuclear transport inhibitor currently in clinical trials as an anti-cancer agent. To determine how selinexor might impact anti-tumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T cell development, a progressive loss of CD8 T cells and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T cell development and function. We determined the minimum concentration of selinexor required to block T cell activation, and showed that T cell inhibitory effects of selinexor occur at levels above 100nM, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 5 day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable to vehicle treated mice. Overall, selinexor treatment leads to transient inhibition of T cell activation but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T cell functioning and development of anti-tumor immunity.

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“…The most recent study pointed out that MSCs can even promote tumor recurrence after stereotactic body radiation therapy [8]. These are believed to be related to the oxidative stress induced by reactive oxygen species ROS, especially •OH (the most toxic form of ROS) [9].…”

Section: Introductionmentioning

confidence: 99%

Sarcandra glabra (Caoshanhu) protects mesenchymal stem cells from oxidative stress: a bioevaluation and mechanistic chemistry

Liu

Lin

et al. 2016

BMC Complement Altern Med

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Background Sarcandra glabra (Caoshanhu) is a traditional Chinese herbal medicine used for treating various oxidative-stressed diseases. The present work evaluated its protective effect on mesenchymal stem cells (MSCs) from oxidative stress and then discussed possible mechanisms underlying this observation.MethodsEthanolic extract of S. glabra (ESG) was investigated by chemical methods for its content of total phenolics, rosmarinic acid, and astilbin. ESG, along with rosmarinic acid and astilbin, was investigated for the effect on the viability of Fenton-treated MSCs using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The observed cell protective effect was further explored by mechanistic chemistry using various antioxidant assays, including DNA protection, •OH-scavenging, •O2 −-scavenging, FRAP (ferric ion reducing antioxidant power), ABTS+•-scavenging, DPPH•-scavenging, and Fe2+-chelating assays.ResultsAnalysis of ESG revealed a content of 46.31 ± 0.56 mg quercetin/g total phenolics, 0.78 ± 0.01 % rosmarinic acid, and 3.37 ± 0.01 % astilbin. Results from the MTT assay revealed that three compounds (rosmarinic acid>astilbin>ESG) could effectively increase the survival of Fenton-treated MSCs. Similarly, in •O2 −-scavenging, DPPH•-scavenging, and Fe2+-chelating assays, rosmarinic acid exhibited more activity than astilbin; while in FRAP, ABTS+•-scavenging assays, astilbin was stronger than rosmarinic acid.Conclusion S. glabra can prevent MSCs from •OH-induced oxidative stress. Such protective effect can be attributed to its antioxidant ability and the presence of two kinds of phytophenols, i.e. caffeoyl derivatives and flavonoids. As the respective representatives of caffeoyl derivatives and flavonoids, rosmarinic acid and astilbin may exert the antioxidant action via direct ROS-scavenging and indirect ROS-scavenging (i.e. Fe2+-chelating). The direct ROS-scavenging ability involves hydrogen atom transfer (HAT) and/or electron transfer (ET) pathway. Astilbin engages the latter pathway more, which can be attributed to the larger planar conjugation in A/C fused rings. Rosmarinic acid, on the other hand, shows more HAT and Fe2+-chelating potential, which may be due to rosmarinic acid bearing one more catechol moiety whereas astilbin has steric-hindrance from 3-α-L-rhamnose and an H-bonding between 4,5 sites. The antioxidant features of rosmarinic acid can be generalized to other caffeoyl derivatives, while that of astilbin cannot be generalized to other flavonoids because of the difference in chemical structures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1383-7) contains supplementary material, which is available to authorized users.

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Mesenchymal stem cells generate pericytes to promote tumor recurrence via vasculogenesis after stereotactic body radiation therapy

Cited by 72 publications

References 56 publications

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy

Sarcandra glabra (Caoshanhu) protects mesenchymal stem cells from oxidative stress: a bioevaluation and mechanistic chemistry

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