Tumor Progression Is Mediated by Thymosin-β4 through a TGFβ/MRTF Signaling Axis

Morita, Tsuyoshi; Hayashi, Ken’ichiro

doi:10.1158/1541-7786.mcr-17-0715

Cited by 39 publications

(33 citation statements)

References 46 publications

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“…This indicates the ability of the vaccine to activate the immune system and limit glioma progression. We found that thymosin, a hormone that stimulates T-cell maturation, 23 demonstrated weak antitumor effect in the rat glioma models. A slight increase in peripheral and tumor-infiltrating CD4+ T cells, but not in CD8+ T and NK cells, was observed in the thymosin treatment group.…”

Section: Discussionmentioning

confidence: 91%

<p>A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model</p>

Li¹,

Zeng²,

He³

et al. 2020

OTT

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Background: Conventional immunotherapy for glioma is not only expensive but also demonstrates less-than-desired clinical efficacy. In this study, we evaluated the immunotherapeutic efficacy of a tumor cell lysate-based hybrid glioma vaccine developed using a molecular-based approach. Methods: First, the ability of the autologous (9L-cell lysate) and allogeneic (C6-cell lysate) vaccines against glioma, individually and in combination, to activate Fischer344 rat dendritic cells (DCs) was determined. Next, the activated DCs were co-cultured with T lymphocytes and screened for the optimal DC-toT cell ratio. The in vitro efficacy of the DC/T-cell vaccine formulations subjected to different immunogen treatments and co-cultured with glioma cells was evaluated based on glioma cell viability and monocyte chemoattractant protein (MCP)-2 and interferon (IFN)-γ secretion. Subsequently, the efficacy of the 9L + C6 hybrid vaccine was evaluated in 32 glioma rat models, randomly allocated to the following five treatment groups: blank control, tumor, vaccine treatment, thymosin treatment, and vaccine + thymosin treatment (combined treatment). Changes in survival duration, intracranial tumor volume, peripheral blood immune-cell (CD4+ T, CD8+ T, and natural killer [NK] cell) count, and serum cytokine (interleukin [IL]-2, IL-10) levels were assessed in these groups. Results: The hybrid vaccine demonstrated the highest glioma cell apoptosis and the lowest cell viability and promoted MCP-2 and IFN-γ secretion in vitro. The vaccine treatment and combined treatment groups demonstrated longer survival duration, lower intracranial tumor volume, and higher immune cell glioma tissue infiltration and IL-2 secretion than the untreated tumor group, indicating the vaccine's good in vivo efficacy. Thymosin treatment had minimal effect in enhancing anti-glioma immunity. Conclusion: We demonstrated the feasibility of combining autologous and allogeneic tumor cell lysates to stimulate specific host cell immune response against glioma cells. The good clinical efficacy of our developed glioma hybrid vaccine in rat models suggests its potential clinical application.

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Section: Discussionmentioning

confidence: 91%

<p>A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model</p>

Li¹,

Zeng²,

He³

et al. 2020

OTT

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“…The function of the five proteins is related to the progress of tumor cell biology. Out of these five proteins, DCP1A regulates Atg12 and is linked to autophagy and proteasome degradation pathways [40], TMSB4X regulates TGFβ1 and participates in the progression of cancer [41], MGST3 increases in the LT97 adenoma cells and participates in cancer development [42], AKR1C2 is a key enzyme in the process of progesterone metabolism and is closely related to gynecological tumor development [43], and ERLIN1 is influences the survival time of pancreatic cancer patients [44].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Xia

Cai

2020

Cell Mol Biol Lett

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Background: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown. Material and methods: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion. Results: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actinmyosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV. Conclusions: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer.

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“…In this regard, Thymosin-ß4 (Tß4; TMSB4X) and THBS1 are considered as tumor promoters with a poor prognosis in different types of cancers (25)(26)(27)(28). Interestingly, TMSB4X has a function in the TGF-ß/Tß4/MRTF signaling pathway, leading to EMT induction and metastasis (36). SRSF6 behaves as an oncogene protein and is associated with proliferation, transformation, and tumorigenicity of immortal cancer cells (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Stage-Associated PBMC Biomarkers in Breast Cancer Using MS-Based Proteomics

et al. 2020

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Background: It is well-described that the transcriptome of peripheral blood mononuclear cells (PBMCs) can be altered in the context of many malignancies to allow them avoid the effective immune response, which leads to cancer invasiveness. Here, we used an MS-based strategy to discover biomarkers in the PBMCs of breast cancer (BC) patients and validated them at different stages of BC. Methods: PBMCs were isolated from the breast cancer patients and were cultured alone or co-cultured with breast cancer cell lines. The role of PBMC in the invasion property of breast cancer cells was explored. NF-kB activity was also measured in the co-cultured breast cancer cells. Identification of protein profiles in the secretome and proteome of the co-cultured PBMCs was performed using SWATH mass spectrometry. Pathway enrichment and gene ontology analyses were carried out to look for the molecular pathways correlated with the protein expression profile of PBMCs in the breast cancer patients. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the candidate genes in the PBMC fraction of the breast cancer patients at the primary and metastatic stages. In silico survival analysis was performed to assess the potential clinical biomarkers in these PBMC subtypes. Results: PBMCs could significantly increase the invasion property of the BC cells concomitant with a decrease in E-cadherin and an increase in both Vimentin and N-cadherin expression. The NF-kB activity in the BC cells significantly increased following co-culturing implying the role of PBMCs in EMT induction. Enrichment analysis showed that the differentially expressed proteins in PBMCs are mainly associated with IL-17, PI3K-Akt, and HIF-1 signaling pathway, in which a set of seven proteins including TMSB4X, HSPA4, S100A9, SRSF6, THBS1, CUL4A, and CANX were frequently expressed. Finally, in silico analysis confirmed that a gene set consisting of S100A9, SRSF6, THBS1, CUL4A, and CANX were found to provide an insight for the identification of metastasis in breast cancer patients. Moradpoor et al. Stage-Associated PBMC Biomarkers, BCs Conclusion: In conclusion, our study revealed that the protein expression profile in PBMCs is a reflection of the proteins expressed in the BC tissue itself; however, the abundance level is different due to the stage of cancer.

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Tumor Progression Is Mediated by Thymosin-β4 through a TGFβ/MRTF Signaling Axis

Cited by 39 publications

References 46 publications

<p>A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model</p>

<p>A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model</p>

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Identification and Validation of Stage-Associated PBMC Biomarkers in Breast Cancer Using MS-Based Proteomics

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