TIM-3 expression in human osteosarcoma: Correlation with the expression of epithelial-mesenchymal transition-specific biomarkers

Shang, Yongjun; Li, Zhanyong; Li, Hong; Xia, Haibo; Lin, Zhenhua

doi:10.3892/ol.2013.1410

Cited by 53 publications

(40 citation statements)

References 30 publications

(32 reference statements)

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“…Therefore, in this study, we tested for Tim-3 expression in osteosarcoma tissue samples by immunohistochemistry and RT-PCR. Our results were in accordance with those obtained by Shang et al (2013); that is Tim-3 mRNA and protein expression was obviously higher in osteosarcoma tissues than that in the adjacent normal tissue, suggesting a close association between Tim-3 expression and the occurrence of osteosarcoma. Dardalhon et al (2010) reported that breast tumor growth was restrained in Tim-3-deficient mice, and that the Tim-3 monoclonal antibody significantly inhibited the EL4 subcutaneous lymphoma growth in mice.…”

Section: Discussionsupporting

confidence: 82%

“…The results indicated a significant decrease in the proliferation and invasive capacities of MG-63 cells. Taken together with the results obtained by Shang et al (2013), this revealed that Tim-3 is co-expressed with various EMT-related proteins, including vimentin, Slug, Snail, and Smad, in osteosarcoma tissues, which contributes to the increased invasiveness of cancer cells. Tim-3 promotes melanoma cell (B16) invasion by elevating the NF-kB activity, leading to melanoma metastasis (Wu et al, 2010).…”

Section: Discussionmentioning

confidence: 75%

“…Tumors with high Tim-3 expression have been reported to present a higher metastatic potential and lower overall survival, suggesting a close association between Tim-3 expression and tumor occurrence and metastasis. (Shang et al, 2013) Moreover, immunohistochemical analysis and double-immunofluorescence staining in 9 human osteosarcoma tissues revealed that Tim-3 was distributed in the cytoplasm and cell membrane of these tissues (Shang et al, 2013), and was also shown to be widely expressed in CD68 + macrophages, CD31 + endothelial cells, CK-18 + epidermal cells, and PCNA + cancer cells. Therefore, in this study, we tested for Tim-3 expression in osteosarcoma tissue samples by immunohistochemistry and RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…Cao et al (2013) found that siRNA Tim-3 suppressed the invasive abilities of cervical cancer cell lines HeLa and SiHa, and concluded that disrupted Tim-3 expression could lead to suppressed tumor cell metastasis (Cao et al, 2013). Another study reported that Tim-3 is co-expressed with epithelial-mesenchymal transition (EMT)-related proteins in the cytoplasm and cell membrane of the osteosarcoma tissue (Shang et al, 2013). Based on the results of these studies, we speculated that Tim-3 was closely associated with osteosarcoma occurrence and metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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“…Oct-3/4 is transcription factor of the POU family. At the early stage, the Oct-3/4 is mainly expressed in the endoderm, and associated with the pluripotent maintenance of embryonic stem cells, with the growth of the embryo, its expression level gradually decreases (18)(19)(20). The gene expression of nanog is not commonly found in somatic cells, and the activation of the gene is vital for the control of self-renewal and the pluripotency of embryonic stem cells (21).…”

Section: A B C D E F Discussionmentioning

confidence: 99%

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

Zhao

Dai

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to investigate the effect of programmed cell death 1 (PD-1) on osteosarcoma (OD) stem cells and T cells, and to determine their correlation. OS stem cells were sorted and identified from OS MG63 cells. Flow cytometry was used to detect the PD-1 expression of the OS tumor stem cell membrane surface. The expression of PD-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). MTT was used to detect the effect of PD-1 signals on T-cell proliferation. The results indicated that the cancer cells (cultured in DMEM medium containing 10% fetal bovine serum) exhibited clear proliferation within 1 week of cell culture, which showed their strong proliferation and aggressive ability. The formation of tumor cell spheres was dependent on the support of serum nutrition. The proliferation of MG63 cells in the serum culture medium was significantly higher than the number of OS cell spheres in serum-free suspension culture (P<0.05). Pluripotent stem cells in cancer cell spheres exhibited significantly higher cluster of differentiation 133 expression compared with the MG63 cells. The PD-1 expression levels of the cancer cell spheres was significantly increased compared with the MG63 cells, which is consistent with the results of the RT-PCR. In conclusion, the MG63 cell line possesses the features of OS stem cells. The MG63 cell line can express the certain cancer-associated cell markers. The expression of PD-1 in spheres was also increased significantly compared to the MG63 cells, which can reduce the immune function of patients and may be closely associated with the occurrence and development of tumors.

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Abnormal expression of Tim‐3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients

et al. 2016

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T‐cell immunoglobulin and mucin‐domain‐3‐containing molecule 3 (TIM‐3) plays a pivotal role in immune regulation and has been found in various tumors. However, the prevalence and distribution of Tim‐3 in osteosarcoma (OS) is still unclear. The aim of this study was to investigate the prevalence and distribution of Tim‐3 in OS. Tim‐3 on peripheral T cells from 82 OS patients and 60 healthy controls were examined by flow cytometry. Plasma levels of IL‐2, IFN‐γ, and TNF‐α were measured by ELSIA. Tim‐3 on both CD4 + T and CD8 + T cells were significantly upregulated in OS patients compared with healthy controls, Tim‐3 + CD4 + T, and Tim‐3 + CD8 + T cells were both negatively associated with serum levels of IL‐2 and IFN‐γ and TNF‐α. In addition, Tim‐3 showed similar levels in patients with different tumor sites. Nevertheless, patients with advanced tumor stage, metastasis, and pathological tumor fracture displayed significantly higher Tim‐3 on both CD4 + T cells and CD8 + T cells than those with early tumor stage, without metastasis and pathological tumor fracture. Moreover, high Tim‐3 on peripheral CD4 + T cells or CD8 + T were significantly related to poor overall survival ( P = 0.014, P = 0.035, respectively). In conclusion, Tim‐3 may be a potential diagnostic and prognostic biomarker for OS progression.

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TIM-3 expression in human osteosarcoma: Correlation with the expression of epithelial-mesenchymal transition-specific biomarkers

Cited by 53 publications

References 30 publications

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

Abnormal expression of Tim‐3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients

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