Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab

Hosseini, Rozita; Asef-Kabiri, Leila; Sarvnaz, Hamzeh; Ghanavatinejad, Alireza; Rezayat, Fatemeh; Hosseini-Ghatar, Reza; Akbari, Mohammad Esmaeil

doi:10.1007/s12094-022-02925-5

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…Dimethyl amiloride (DMA), GW4869, and a glucosyl ceramide synthase inhibitor have been reported to inhibit EV secretion in several cell lines. 59 Among them, we selected GW4869, a selective neutral sphingomyelinase (N-SMase) inhibitor. Our validation indeed showed that the action of GW4869 on HNSCC cells clearly suppressed EV secretion at the protein level (Figure 4A).…”

Section: Discussionmentioning

confidence: 99%

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Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system

Ogawa,

Ono,

Ryumon

et al. 2024

Head & Neck

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BackgroundCisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP‐resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC.MethodsWe established CDDP‐resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression.ResultsThe CDDP‐resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell‐killing effect.ConclusionsEVs were involved in the ATP7B‐mediated mechanism underlying CDDP resistance. Further clarification of the EV‐induced CDDP‐resistance mechanism may lead to novel therapeutic strategies for HNSCC.

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Section: Discussionmentioning

confidence: 99%

“…Dimethyl amiloride (DMA), GW4869, and a glucosyl ceramide synthase inhibitor have been reported to inhibit EV secretion in several cell lines 59 . Among them, we selected GW4869, a selective neutral sphingomyelinase (N‐SMase) inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system

Ogawa,

Ono,

Ryumon

et al. 2024

Head & Neck

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show abstract

“…The list of sEV biogenesis, release, and uptake is provided in Tables 3 and 4. Notably, compounds like GW4869 and manumycin A have demonstrated the ability to inhibit neutral sphingomyelinase 2 (nSMase2) [43,44], a key enzyme in the ceramide-dependent pathway of sEV release [15]. Other SMIs such as nSMase 2 inhibitor 2,6-dimethoxy-4-(5-phenyl-4-thiophen-2-yl-1H-imidazole-2-yl)-phenol (DPTIP), antidiabetic medication glibenclamide, antidepressant imipramine, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin, insulin secretion inducer dimethyl amiloride (DMA), antifungal agent ketoconazole, proton-pump inhibitor omeprazole and cannabis-derived compound cannabidiol are examples of sEV release inhibitors (reviewed in [45]).…”

Section: Small Molecule Inhibitors For Targeting Sev Releasementioning

confidence: 99%

Decoding the secrets of small extracellular vesicle communications: exploring the inhibition of vesicle-associated pathways and interception strategies for cancer treatment

Shams

2024

Am J Cancer Res

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Cancer disease is the second leading cause of death worldwide. In 2023, about 2 million new cancer cases and 609,820 cancer deaths are projected to occur in the United States. The driving forces of cancer progression and metastasis are widely varied and comprise multifactorial events. Although there is significant success in treating cancer, patients still present with tumors at advanced stages. Therefore, the discovery of novel oncologic pathways has been widely developed. Tumor cells communicate with each other through small extracellular vesicles (sEVs), which contribute to tumor-stromal interaction and promote tumor growth and metastasis. sEV-specific inhibitors are being investigated as a next-generation cancer therapy. A literature search was conducted to discuss different options for targeting sEV pathways in cancer cells. However, there are some challenges that need to be addressed in targeting sEVs: i) specificity and toxicity of sEV inhibitor, ii) targeted delivery of sEV inhibitors, iii) combination of sEV inhibitors with current standard chemotherapy to improve patients' clinical outcomes, and iv) data reproducibility and applicability at distinct levels of the disease. Despite these challenges, sEV inhibitors have immense potential for effectively treating cancer patients.

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“…The tumor lytic potential of the CB-HSC-derived-NK cells against K562 and MCF-7 cell lines was measured by XTT (Sigma) assay as described elsewhere (12,13). In this regard, 0.25 mg/mL of XTT solution was prepared in PBS.…”

Section: Nk Cell-mediated Cytotoxicity Assaymentioning

confidence: 99%

Cytokine-Treated Natural Killer Cells Derived from Cord Blood Haematopoietic Stem Cells Exhibit Potential Cytotoxicity Against Cancer Cells

Hosseini,

Ahmadvand,

et al. 2024

Int J Cancer Manag

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Background: Despite substantial efforts to leverage natural killer (NK) cells in cancer immunotherapy, challenges associated with limited cell numbers and sources persist. In this study, our objective is to differentiate NK cells from cord blood hematopoietic stem cells (CB-HSCs) and assess their anti-tumor effects. Methods: Cord blood samples were obtained from pregnant women undergoing normal delivery. Mononuclear cells (MNC) were isolated by gradient centrifugation. Subsequently, HSCs were isolated using the MACs cell separation kit. The isolated HSCs were cultured in NK cell differentiation and expansion media for 21 days and 7 days, respectively. The NK cells were examined for expression of activating markers, cytokine secretion and cytolytic effects by flow cytometry, ELISA and XTT tests, respectively. Results: High-purity HSCs and NK cells were obtained in this study. The CB-HSCs-derived NK cells exhibited significantly higher expression of NKG2D, NKp30, NKp44 and NKp46 receptors (at day 28 of treatment) after treatment by IL-15 and IL-2, compared to the early differentiated NK cells (day 21). NK cells derived from CB-HSCs treated with the combination of IL-15 and IL-2 could robustly lyse breast cancer MCF-7 and K562 cells. Also, the obtained NK cells were able to release higher amounts of TNF-α and IFN-γ cytokines in response to tumor cell experiences. Conclusions: Our findings showed that functionally active CB-HSCs-derived NK cells can be successfully generated ex vivo using a cytokine cocktail without a need for stroma for potential use in the cancer immunotherapy.

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Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab

Cited by 8 publications

References 46 publications

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system

Decoding the secrets of small extracellular vesicle communications: exploring the inhibition of vesicle-associated pathways and interception strategies for cancer treatment

Cytokine-Treated Natural Killer Cells Derived from Cord Blood Haematopoietic Stem Cells Exhibit Potential Cytotoxicity Against Cancer Cells

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