Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway

Yang, Jian; Hu, Yong; Wang, Lu; Sun, Xiangran; Yu, Ling; Guo, Weichun

doi:10.1080/21655979.2021.2005220

Cited by 10 publications

(10 citation statements)

References 38 publications

(38 reference statements)

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“…When DAPT was tested in a mouse para‐tibial tumor model of OS, a K7M2 cell line, and a lung metastasis model, it inhibited ERK pathway phosphorylation by suppressing Notch activation to effectively suppress tumor growth, angiogenesis, and lung metastasis, thereby improving patient survival 239 . Another γ‐secretase inhibitor, RO4929097, reversed the effects of human umbilical vascular endothelial cell‐derived exosomes on Notch 1, Hes 1, and Hey 1 expression by inhibiting the Notch1 signaling pathway 240 . A novel DNA methyltransferase 1 (DNMT‐1) small‐molecule antagonist/inhibitor, named DI‐1 (DNMT‐1 inhibitor), enhances the antitumor effects of the molecularly targeted drug cabozantinib in OS cell lines 241 .…”

Section: Mechanism Of Targeting Signaling Pathwaysmentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb‐preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β‐catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD‐1/PD‐L1, MAPK, and NF‐κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway‐based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

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Section: Mechanism Of Targeting Signaling Pathwaysmentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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“…A study found that inhibition of NOTCH1 signaling significantly restrained the growth of CSCs in osteosarcoma [ 46 , 47 ]. Exosomes from human umbilical vein endothelial cells promoted the self-renewal of CSCs in osteosarcoma by enhancing the expression of NOTCH1, Hes1, and Hey1 while blocking NOTCH signaling reversed the positive effect on the CSCs [ 48 ]. In addition, studies have reported that the activation of NOTCH1 signaling induced by cisplatin promoted the activity of CSCs in osteosarcoma in vitro, including increasing the number of Stro-1+/CD117+ double-positive cells and spheroid formation capacity [ 49 ].…”

Section: Effect Of the Notch Signaling Pathway On Osteosarcomamentioning

confidence: 99%

NOTCH Signaling in Osteosarcoma

Zhang

Shao

2023

CIMB

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The combination of neoadjuvant chemotherapy and surgery has been promoted for the treatment of osteosarcoma; however, the local recurrence and lung metastasis rates remain high. Therefore, it is crucial to explore new therapeutic targets and strategies that are more effective. The NOTCH pathway is not only involved in normal embryonic development but also plays an important role in the development of cancers. The expression level and signaling functional status of the NOTCH pathway vary in different histological types of cancer as well as in the same type of cancer from different patients, reflecting the distinct roles of the Notch pathway in tumorigenesis. Studies have reported abnormal activation of the NOTCH signaling pathway in most clinical specimens of osteosarcoma, which is closely related to a poor prognosis. Similarly, studies have reported that NOTCH signaling affected the biological behavior of osteosarcoma through various molecular mechanisms. NOTCH-targeted therapy has shown potential for the treatment of osteosarcoma in clinical research. After the introduction of the composition and biological functions of the NOTCH signaling pathway, the review paper discussed the clinical significance of dysfunction in osteosarcoma. Then the paper reviewed the recent relevant research progress made both in the cell lines and in the animal models of osteosarcoma. Finally, the paper explored the potential of the clinical application of NOTCH-targeted therapy for the treatment of osteosarcoma.

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“…Conversely, osteosarcoma cells themselves are also capable of inducing MSC differentiation into CAFs through Notch/Akt signaling [ 193 ]. Endothelial cells secreting exosomes are also promoters of osteosarcoma stemness through Notch signaling [ 194 ].…”

Section: Mechanisms Of Csc Resistance To Conventional Therapiesmentioning

confidence: 99%

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters

Martins-Neves

Sampaio-Ribeiro

2022

IJMS

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Osteosarcoma is amongst the most prevalent bone sarcomas and majorly afflicts children and adolescents. Therapeutic regimens based on the triad of doxorubicin, cisplatin and methotrexate have been used as the state-of-the-art approach to clinical treatment and management, with no significant improvements in the general outcomes since their inception in the early 1970s. This fact raises the following problematic questions: Why do some patients still relapse despite an initial good response to therapy? Why do nearly 30% of patients not respond to neoadjuvant therapies? Does residual persistent disease contribute to relapses and possible metastatic dissemination? Accumulating evidence suggests that chemoresistant cancer stem cells may be the major culprits contributing to those challenging clinical outcomes. Herein, we revisit the maneuvers that cancer stem cells devise for eluding cell killing by the classic cytotoxic therapies used in osteosarcoma, highlighting studies that demonstrate the complex crosstalk of signaling pathways that cancer stem cells can recruit to become chemoresistant.

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Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating Notch signaling pathway

Cited by 10 publications

References 38 publications

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

NOTCH Signaling in Osteosarcoma

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters

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