Heparan sulfate analogues regulate tumor-derived exosome formation that attenuates exosome functions in tumor processes

Wu, Xiao‐Tao; Kang, Mingzhu; Wang, Danhui; Zhu, Min; Hu, Yiwei; Zhang, Yan; Deng, Chao; Chen, Jinghua; Teng, Liping

doi:10.1016/j.ijbiomac.2021.07.110

Cited by 10 publications

(9 citation statements)

References 45 publications

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“…Since most of the key regulators were found to be overexpressed and/or hyperactivated in tumor cells, they may serve as potential candidates for TDE inhibition. Wu et al indicated that heparan sulfate (HS) analogs (heparin, low molecular weight heparin, and 6-O-desulfated heparin) specifically and efficiently inhibited TDE secretion by targeting Syndecan-Syntenin-Alix, leading to weakened tumor proliferation and invasion 109 . When B16F10 melanoma cells were treated with different HS analogs, both TDE secretion and protein cargo were inhibited.…”

Section: Inhibition Strategies For Tdesmentioning

confidence: 99%

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Chen

Duan

et al. 2022

Exp Mol Med

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Mounting evidence indicates that tumor-derived exosomes (TDEs) play critical roles in tumor development and progression by regulating components in the tumor microenvironment (TME) in an autocrine or paracrine manner. Moreover, due to their delivery of critical molecules that react to chemotherapy and immunotherapy, TDEs also contribute to tumor drug resistance and impede the effective response of antitumor immunotherapy, thereby leading to poor clinical outcomes. There is a pressing need for the inhibition or removal of TDEs to facilitate the treatment and prognosis of cancer patients. Here, in the present review, we systematically overviewed the current strategies for TDE inhibition and clearance, providing novel insights for future tumor interventions in translational medicine. Moreover, existing challenges and potential prospects for TDE-targeted cancer therapy are also discussed to bridge the gaps between progress and promising applications.

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Section: Inhibition Strategies For Tdesmentioning

confidence: 99%

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Chen

Duan

et al. 2022

Exp Mol Med

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“…Preclinical studies have revealed that SST0001 in combination with dexamethasone exerts a significant anti-tumor effect in multiple myeloma xenograft mouse models, markedly reducing the subcutaneous growth of different multiple myeloma cell lines ( Ritchie et al, 2011 ). Importantly, as both SDC-1 and heparanase participate in exosome generation, heparanase inhibition reduces tumor growth as well as exosome-derived tumor recurrence ( Wu et al, 2021 ). The inhibition of proteolysis in the ED of SDC-1 is another method that targets SDC-1 shedding.…”

Section: Perspectives For Therapeutic Intervention Targeting Sdc-1mentioning

confidence: 99%

The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance

Guo

Lei

et al. 2022

Front. Cell Dev. Biol.

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Metastasis and relapse are major causes of cancer-related fatalities. The elucidation of relevant pathomechanisms and adoption of appropriate countermeasures are thus crucial for the development of clinical strategies that inhibit malignancy progression as well as metastasis. An integral component of the extracellular matrix, the type 1 transmembrane glycoprotein syndecan-1 (SDC-1) binds cytokines and growth factors involved in tumor microenvironment modulation. Alterations in its localization have been implicated in both cancer metastasis and drug resistance. In this review, available data regarding the structural characteristics, shedding process, and nuclear translocation of SDC-1 are detailed with the aim of highlighting strategies directly targeting SDC-1 as well as SDC-1-mediated carcinogenesis.

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“…Overcoming EV-mediated immune escape by blocking TEVs’ release or inhibiting their uptake may represent an additional therapeutic approach in cancer. For example, heparin has been shown to inhibit cellular uptake of TEVs with subsequent reduction of tumor cell migration, adhesion and inhibition of tumor growth and metastasis in several cancer models [ 215 , 216 , 217 ]. Further evaluation of heparin-based TEV-targeting may provide new opportunities for inhibiting immune escape.…”

Section: Translational Applications: Targeting Ev-mediated Tumor Immu...mentioning

confidence: 99%

Extracellular Vesicles and Their Roles in the Tumor Immune Microenvironment

Reale

Khong

Spencer

2022

JCM

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Tumor cells actively incorporate molecules (e.g., proteins, lipids, RNA) into particles named extracellular vesicles (EVs). Several groups have demonstrated that EVs can be transferred to target (recipient) cells, making EVs an important means of intercellular communication. Indeed, EVs are able to modulate the functions of target cells by reprogramming signaling pathways. In a cancer context, EVs promote the formation of a supportive tumor microenvironment (TME) and (pre)metastatic niches. Recent studies have revealed that immune cells, tumor cells and their secretome, including EVs, promote changes in the TME and immunosuppressive functions of immune cells (e.g., natural killer, dendritic cells, T and B cells, monocytes, macrophages) that allow tumor cells to establish and propagate. Despite the growing knowledge on EVs and on their roles in cancer and as modulators of the immune response/escape, the translation into clinical practice remains in its early stages, hence requiring improved translational research in the EVs field. Here, we comprehensively review the current knowledge and most recent research on the roles of EVs in tumor immune evasion and immunosuppression in both solid tumors and hematological malignancies. We also highlight the clinical utility of EV-mediated immunosuppression targeting and EV-engineering. Importantly, we discuss the controversial role of EVs in cancer biology, current limitations and future perspectives to further the EV knowledge in clinical practice.

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Heparan sulfate analogues regulate tumor-derived exosome formation that attenuates exosome functions in tumor processes

Cited by 10 publications

References 45 publications

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance

Extracellular Vesicles and Their Roles in the Tumor Immune Microenvironment

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