Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

Barooei, Roghayeh; Mahmoudian, Reihaneh Alsadat; Abbaszadegan, Mohammad Reza; Mansouri, Atena; Gholamin, Mehran

doi:10.1007/s12032-015-0653-4

Cited by 40 publications

(24 citation statements)

References 52 publications

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“…It is also possible that TSLP may redirect metastasis to other sites beside the lung, including metastasis to lymph nodes, which warrant further investigation. This is consistent with a study in human gastric carcinoma, 53 which showed a significant relationship between TSLP overexpression and metastasis to lymph nodes. Thus, from a conceptual standpoint, our work may have broader implications in cancer types, independent of their origin, that overproduce TSLP.…”

Section: Discussionsupporting

confidence: 93%

Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism

et al. 2018

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It is well-recognized that macrophages, which arise from circulating precursors, enhance tumor progression in patients and animal models. However, less is known regarding the role of tissue-resident macrophages in metastasis. Moreover, the identification of tumor factors which influence macrophage function in the metastatic niche remains incomplete. Here, we investigated one such cytokine known as thymic stromal lymphopoietin (TSLP). Our rationale to focus on TSLP was based on two non-overlapping findings; first, TSLP exacerbates asthma in part by altering the lung macrophage response and, secondly, TSLP is produced by certain mouse and human tumor systems, although its role in neoplasia remains understudied. Thus, we tested the hypothesis that tumor-derived TSLP augments lung metastasis by rendering alveolar macrophages pro-tumorigenic. To test this hypothesis, we principally employed the 4T1 tumor model, which produces high levels of TSLP and metastasizes to the lung. TSLP loss-of-function significantly reduced spontaneous lung metastasis, as well as lung colonization. Moreover, similar outcomes were observed in both wild-type and immune-deficient hosts, suggesting that TSLP acted on innate immune cells such as macrophages. To test this notion, pharmacologic depletion of alveolar macrophages significantly reduced lung tumor growth of the TSLP-expressing, but not TSLP-deficient tumor population. In contrast, depleting macrophages originating from the circulation did not impact lung tumor growth. Lastly, TSLP increased the invasive and angiogenic gene expression profile of the alveolar macrophage population. Altogether, our study identified a novel TSLP-alveolar macrophage axis in lung metastasis, which offers new insights into mechanisms of metastasis and potential therapeutic targets.

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Section: Discussionsupporting

confidence: 93%

Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism

et al. 2018

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“…In addition, expression of TSLP, IL6, GBP1, CD274, TNFSF13B, OASL, and pnpla3 involved in the immune system, cell cycle, T-cell activation and lymphocyte's proliferation were also altered in THP1 cells by toxin treatment. Dysregulation of these genes cause increased apoptosis, cellular division and cancerous activities (Dong et al, 1999 ; Andreoli et al, 2014 ; Barooei et al, 2015 ; Hengeveld and Kersten, 2015 ; Ibsen et al, 2015 ; Manda et al, 2015 ; Ali et al, 2016 ). We performed motif enrichment to predict the transcription factor binding sites and over-represented regions of these cancer-related genes to better understand the complex biological mechanism.…”

Section: Discussionmentioning

confidence: 99%

Simulation Study of cDNA Dataset to Investigate Possible Association of Differentially Expressed Genes of Human THP1-Monocytic Cells in Cancer Progression Affected by Bacterial Shiga Toxins

et al. 2018

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Shiga toxin (Stxs) is a family of structurally and functionally related bacterial cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively. Until recently, it has been thought that Stxs only inhibits the protein synthesis and induces expression to a limited number of genes in host cells, but recent data showed that Stxs can trigger several signaling pathways in mammalian cells and activate cell cycle and apoptosis. To explore the changes in gene expression induced by Stxs that have been shown in other systems to correlate with cancer progression, we performed the simulated analysis of cDNA dataset and found differentially expressed genes (DEGs) of human THP1-monocytic cells treated with Stxs. In this study, the entire data (treated and untreated replicates) was analyzed by statistical algorithms implemented in Bioconductor packages. The output data was validated by the k-fold cross technique using generalized linear Gaussian models. A total of 50 DEGs were identified. 7 genes including TSLP, IL6, GBP1, CD274, TNFSF13B, OASL, and PNPLA3 were considerably (<0.00005) related to cancer proliferation. The functional enrichment analysis showed 6 down-regulated and 1 up-regulated genes. Among these DEGs, IL6 was associated with several cancers, especially with leukemia, lymphoma, lungs, liver and breast cancers. The predicted regulatory motifs of these genes include conserved RELA, STATI, IRFI, NF-kappaB, PEND, HLF, REL, CEBPA, DI_2, and NFKB1 transcription factor binding sites (TFBS) involved in the complex biological functions. Thus, our findings suggest that Stxs has the potential as a valuable tool for better understanding of treatment strategies for several cancers.

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“…Recent studies have also implicated cancer tissue TSLP expression and serum TSLP level were significantly increased [15,21] . Moreover, the role of TSLP in tumor growth and metastasis is supported by many studies [14,22,23] . Consistent with these studies, we found that breast cancer cell lines have more expression and secretion than normal breast epithelium.…”

Section: Discussionmentioning

confidence: 92%

TSLP-mediated inflammatory factors production contributes to metastatic breast cancer-induced bone cancer pain in mice

Xian

Wang

et al. 2018

Preprint

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Objective: Metastatic breast cancer-induced bone cancer pain (BCP) is one of the most disabling factors in patients suffering. Recent studies show thymic stromal lymphopoietin (TSLP) is a proinflammatory factor and high expression in cancer cells. Here we investigated whether and how TSLP released form breast cancer cells contributes to BCP. Methods: Braset cancer cells MDA-MB-231 were intramedullary injected into the femur to induce BCP, TSLP neutralizing antibody was intrathecally injected and pain hypersensitivity was checked by behavioral testing. The TSLP expression was knockdown by shRNA. Human TSLP, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 in intramedullary space of the femur of rats was detected by ELISA. Results: TSLP neutralizing antibody intrathecally injection significantly reduced MDA-MB-231 cells inoculation induced persistent mechanical allodynia and heat hyperalgesia and TSLP increased. Furthermore, Persistent mechanical allodynia and heat hyperalgesia of mice models were also decreased in MDA-MB-231 cells with TSLP knockdown. Finally, some inflammatory factors, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 were significantly elevated in the intramedullary space lavage fluid of the right femur after cancer cell inoculation, but were obviously reduced in models with neutralizing antibody of TSLP treatment and TSLP knockdown. Conclusion: TSLP-mediated inflammatory factors release contributes to the maintenance of tumoral hypersensitivity. Inhibition of the TSLP may provide a new therapy for BCP management.

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Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer

Cited by 40 publications

References 52 publications

Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism

Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism

Simulation Study of cDNA Dataset to Investigate Possible Association of Differentially Expressed Genes of Human THP1-Monocytic Cells in Cancer Progression Affected by Bacterial Shiga Toxins

TSLP-mediated inflammatory factors production contributes to metastatic breast cancer-induced bone cancer pain in mice

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