論文 - 詳細
| RRC ID | 65411 |
|---|---|
| 著者 | Takeda T, Tsubak M, Genno S, Matsuda T, Yamamoto Y, Ueda E, Imano M, Satou T, Nishida S. |
| タイトル | CD49d and CD49e induce cell adhesion-mediated drug resistance through the nuclear factor-κB pathway in Burkitt lymphoma. |
| ジャーナル | J Physiol Pharmacol |
| Abstract |
Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin's B-cell lymphoma. Currently, multi-agent chemotherapy regimens are being used to significantly improve cure rates and achieve complete remissions in BL patients. However, drug resistance can often occur within 6 months in BL patients, contributing to poor prognosis. Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy. However, the molecular mechanism underlying CAM-DR in BL has not been identified yet. In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells. We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved. However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells. Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation. In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients. |
| 巻・号 | 71(4) |
| 公開日 | 2020-8-1 |
| DOI | 10.26402/jpp.2020.4.02 |
| PMID | 33214335 |
| MeSH | Animals Antineoplastic Agents / pharmacology* Apoptosis Regulatory Proteins / metabolism Bortezomib / pharmacology Burkitt Lymphoma / drug therapy* Burkitt Lymphoma / immunology Burkitt Lymphoma / metabolism Cell Adhesion / drug effects* Cell Line, Tumor Coculture Techniques Drug Resistance, Neoplasm* Humans Integrin alpha4 / metabolism* Integrin alpha5 / metabolism* Mice Mice, Inbred BALB C NF-kappa B / metabolism* Proteasome Inhibitors / pharmacology Signal Transduction Tumor Microenvironment |
| IF | 2.644 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ST2(RCB0224) |