Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

Fan, Mengke; Zhang, Guochuan; Chen, Wei; Li, Qi; Xie, Mingfang; Zhang, Yue-yao; Zhang, Qi

doi:10.3389/fonc.2021.710689

Cited by 40 publications

(40 citation statements)

References 59 publications

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“…This gave us a hint that p38-MAPK may be involved in the regulation of cell migration and invasion by Ang2. MAPK pathway, as a key signal pathway affecting cell migration and invasion, plays a role by responding to extracellular stimuli [30] . In the process of in ammation, the p38-MAPK signaling pathway has been con rmed to be activated by IL-1β to promote in ammation [12] .…”

Section: Discussionmentioning

confidence: 99%

IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

Pei

Yang

et al. 2022

Preprint

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Background: The migration, proliferation, and inflammatory factor secretion of vascular smooth muscle cells (VSMCs) are involved in the important pathological processes of several vascular occlusive diseases, including coronary atherosclerosis (CAS). IL-1β, as a bioactive mediator of VSMC synthesis and secretion, can promote the pathological progress of CAS. In this study, we further explored the underlying molecular mechanisms by which IL-1β regulates VSMC migration, invasion.Methods: We pretreated A7r5 and HASMC with IL-1β for 24 hours, and measured the expression of IL-1β, PCNA, cyclin D1, MMP2 and MMP9 in the cells by Western blotting. Cell migration and invasion ability were measured by Transwell and wound healing assays. Cell viability was measured by an MTT assay. Results: We found that IL-1β up-regulated the expression of proliferation-related proteins (PCNA and Cyclin D1) in A7r5 and HASMC, and induces the secretion of MMP2 and MMP9, promotes cell invasion and migration. In addition, in A7r5 and HASMCs treated with IL-1β, the expression of Ang2 increased in a time-dependent manner, transfection with si-Ang2 suppressed cell migration and invasion, with down-regulated MMP2 and MMP9 expression. In parallely, we further found that the p38-MAPK pathway is activated in cells induced by IL-1β, p38-MAPK inhibitors can down-regulate the expression of Ang2. Conclusions: These data demonstrated that IL-1β promotes A7r5 and HASMC migration and invasion via the p38-MAPK/Ang2 pathway.

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Section: Discussionmentioning

confidence: 99%

IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

Pei

Yang

et al. 2022

Preprint

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“…TAM-associated Siglec-15 can promote tumor immune escape by suppressing CD8 + T-cell responses and promoting immunosuppressive TME formation through the production of transforming growth factor-β (TGF-β) [ 29 ]. In addition, recent studies have shown that Siglec-15 promotes the malignant progression of osteosarcoma (OS) cells by inhibiting the DUSP1-mediated mitogen-activated protein kinase (MAPK) pathway, and high expression of Siglec-15 is associated with pulmonary metastasis and predicts poor prognosis in OS patients [ 39 ]. Li et al suggested that Siglec-15 presented immunosuppressive relevance in pancreatic ductal adenocarcinoma (PDAC) and was expressed on TAMs and PDAC cells.…”

Section: Expression Spectrum Of Siglecs In Tumorsmentioning

confidence: 99%

The intriguing roles of Siglec family members in the tumor microenvironment

Jiang

Kang³

et al. 2022

Biomark Res

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Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.

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“…Each Siglec preferentially recognizes a different type of sialic acid. Siglec-15, in particular, is selectively expressed in myeloid cells and osteoclasts [45] . While studies in other types of sarcoma are lacking, preclinical studies on osteosarcoma cell lines and xenograft mouse models discovered that downregulation of Siglec-15 led to decreased tumor proliferation by inducing EMT and promotion of DUSP1 [46] .…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

“…Siglec-15, in particular, is selectively expressed in myeloid cells and osteoclasts [ 45 ] . While studies in other types of sarcoma are lacking, preclinical studies on osteosarcoma cell lines and xenograft mouse models discovered that downregulation of Siglec-15 led to decreased tumor proliferation by inducing EMT and promotion of DUSP1 [ 46 ] . Following that finding, an analysis of 36 human osteosarcoma samples also showed that higher expression of Siglec-15 by immunohistochemistry was associated with worse overall survival compared with tumors with low Siglec-15 expression [ 46 ] .…”

Section: Emerging Mechanisms Of Resistancementioning

confidence: 99%

Emerging mechanisms of immunotherapy resistance in sarcomas

Florou¹,

Wilky²

2022

CDR

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Sarcomas are a heterogeneous group of over 150 mesenchymal neoplasms of bone and soft tissue. Clinical prognosis remains poor in the metastatic and refractory setting, despite treatment with traditional chemotherapies. A subset of sarcoma patients can exhibit remarkable responses to novel immune therapies; however, most patients will not respond. Emerging data from genetic and transcriptomic datasets suggests that patients who are resistant to checkpoint inhibitor monotherapy may have low expression of immune-related genes, suggesting that the sarcoma was not sufficiently immunogenic to trigger or maintain an immune response to generate tumor-specific immune effector cells. In this review, we discuss the emerging data surrounding potential mechanisms of resistance, including various biomarkers explored in clinical trials of immune therapy for sarcomas. We also review future directions in clinical trials that are focused on boosting tumor immunogenicity to improve the activity of checkpoint inhibitors, as well as adoptive cellular therapy approaches to bypass deficiencies in neoantigens or antigen presentation.

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Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway

Cited by 40 publications

References 59 publications

IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

The intriguing roles of Siglec family members in the tumor microenvironment

Emerging mechanisms of immunotherapy resistance in sarcomas

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