Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle

Tang, Ke; Hu, Liang; Ma, Jingwei; Zhang, Huafeng; Zhang, Yi; Li, Yong; Ma, Ru; Luo, Shunqun; Liu, Dongbo; Long, Guoxian; Han, Meng; Liu, Shunfang; Song, Anping; Shen, Meizhu; Hu, Guoqing; Huang, Bo

doi:10.1002/stem.2076

Cited by 7 publications

(5 citation statements)

References 26 publications

(32 reference statements)

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“…Notably, the migration to tumor of MDSCs depended mainly on CCL2/CCR2 pathway [ 38 ]. More recently study revealed that, mesenchymal stem-like cells(MSLCs), the progenitor cells of fibroblast and adipocyte, which could migrate to tumor sites and then promote tumor growth, were also recruited by CCL2/CCR2 pathway [ 39 ]. Another article clarified that CCR2 participates in the recruitment of bone marrow-derived fibroblasts into the kidney during the development of renal fibrosis, thus we speculated CCR2 may promote tumor development by recruiting some bone marrow-derived fibroblasts into the tumor sites and then become cancer associated fibroblasts(CAF) in the tumor microenvironment [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

Zhang

Líu

et al. 2016

Oncotarget

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BackgroundBeing a critical chemokine receptor in chemoattracting myeloid cells into tumor tissues, C-C chemokine receptor 2 (CCR2) has been detected in many malignant tumors. This study aims to evaluate the prognostic value of CCR2 expression in patients with gastric cancer after surgery.ResultsCCR2 expression was detected in the accessory cells around gastric cancer cells in a diffused manner. CCR2 high expression was correlated with tumor invasion depth (P=0.006 and P=0.004, respectively), lymph node metastasis (P=0.038 and P=0.011, respectively) and TNM stage (P=0.003 and P=0.001, respectively) in the two independent sets. Multivariate Cox regression analysis identifies CCR2 high expression was an independent poor prognostic factor for OS of patients with gastric cancer in the two sets (P=0.013 and P=0.006, respectively). Integration of CCR2 expression and TNM stage could provide additional prognostic value for OS than TNM stage alone in the two sets (P=0.038 and P=0.002, respectively).MethodsTwo independent sets comprising a total of 474 patients who received standard gastrectomy were enrolled in the study. The expression level of CCR2 was detected by immunohistochemistry. The correlations between CCR2 expression and clinicopathological factors were explored, and the prognostic significance for overall survival (OS) was determined by Kaplan-Meier analysis.ConclusionsCCR2 high expression in the tumor microenvironment is a novel independent unfavorable prognostic factor for patients with gastric cancer. Combination of CCR2 expression and TNM stage could provide a better prognostic model for OS of gastric cancer patients.

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Section: Discussionmentioning

confidence: 99%

High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

Zhang

Líu

et al. 2016

Oncotarget

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“…Recent studies have highlighted the critical role of TRCs in regulating the effect of immune cells on tumors. 8 On the one hand, TRCs themselves effectively evade immune-derived killing by (1) producing immunosuppressive molecules; 9 (2) recruiting immunosuppressive cells; 10 (3) losing antigen processing and presentation machinery and downregulating the expression of MHC I and co-stimulatory molecules. 11 On the other hand, tumorigenic TRCs profoundly reset immune cells, including macrophages and regulatory T cells into tumor-promoting ones.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

et al. 2017

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Stem cell-like tumor-repopulating cells (TRCs) have a critical role in establishing a tumor immunosuppressive microenvironment. However, means to enhance antitumor immunity by disrupting TRCs are absent. Our previous studies have shown that tumor cell-derived microparticles (T-MPs) preferentially abrogate TRCs by delivering antitumor drugs into nuclei of TRCs. Here, we show that low dose irradiation (LDI) enhances the effect of cisplatin-packaging T-MPs (Cis-MPs) on TRCs, leading to inhibiting tumor growth in different tumor models. This antitumor effect is not due to the direct killing of tumor cells but is T cell-dependent and relies on macrophages for their efficacy. The underlying mechanism is involved in therapeutic reprograming macrophages from tumor-promotion to tumorinhibition by disrupting TRCs and curtailing their vicious education on macrophages. These findings provide a novel strategy to reset macrophage polarization and confer their function more like M1 than M2 types with highly promising potential clinical applications.

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“…Several recent published studies investigated ADSCs-MCF-7 communication in vitro. For example, Tang et al (2015) showed that mesenchymal stem cells (MSCs) are recruited to malignant fluids by a tumorcell-derived chemokine-mediated signaling pathway on the MSC. TGF-β can alter tight junction formation in the mammary epithelium and induce a number of embryonic signaling pathways, including the Wnt, Notch, and Hh pathways.…”

Section: Discussionmentioning

confidence: 99%

Interaction of adipose-derived mesenchymal stem cells with MCF-7 cells in vitro:a study emphasizing signaling molecule expression and transcriptional changes

Wu¹,

Jin²,

Chen³

et al. 2017

Turk J Biol

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IntroductionAdipose-derived mesenchymal stem cells (ADSCs) are a heterogeneous population of adult stem cells derived from adipose tissue. ADSCs functionally differentiate into various cell lineages in a special microenvironment (Uzbas et al., 2015). ADSCs are autologous, available in sufficient quantities in most patients, and are widely used in soft tissue repair, for instance, in breast reconstruction in surgical patients (Rowan et al., 2014). However, recent papers indicate ADSCs potentially induce a tumor microenvironment and affect tumor cell biology. In mammary tissue (Muehlberg et al., 2009), resident stem cells promote breast cancer metastasis, home to the tumor site, and stimulate tumor growth not only when coinjected locally but also when injected intravenously. Kucerova et al. (2011) reported that ADSCs could stimulate proliferation of several breast cancer cells in vitro, such as MDA-MB-361, T47D, and EGFP-MCF-7. Kim et al. (2013) found that breast and abdominal adipose tissues have comparable gene expression profiles and are comparable in supporting breast cancer cell proliferation and metastasis. On the other hand, it has been previously reported that the morphology and phenotype of ADSCs are altered when cocultured with tumor cells. ADSCs (Jotzu et al., 2011) that received tumor-derived factors differentiated into carcinoma-associated fibroblast-like cells, which functionally contribute to tumor growth, invasion, and metastasis. ADSCs directly cocultured with H358 lung cancer cells differentiated into tumor stroma that play a supportive role during cancer progression (Park et al., 2013).Of note, except for the diffusible factors (cytokines, chemokine, and growth factors), cell-derived exosomes have been described as a new signal in cell-to-cell communication. Exosomes are membrane vesicles (30-100 nm) from luminal membranes of multivesicular bodies and are constitutively released upon fusion with cell membranes (Tan et al., 2016). It has been previously confirmed that ADSCs secrete exosomes (Cho et al., 2012;Lin et al., 2013), promote MCF-7 cell migration, and that exosomes from breast cancer cells convert ADSCs into myofibroblast-like cells. These results provide evidence that exosomes play a role in crosstalk between ADSCs and MCF-7 cells.

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Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle

Cited by 7 publications

References 26 publications

High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

Interaction of adipose-derived mesenchymal stem cells with MCF-7 cells in vitro:a study emphasizing signaling molecule expression and transcriptional changes

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