Oral Cancer Cells Release Vesicles that Cause Pain.
Oral Cancer Cells Release Vesicles that Cause Pain.
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DOI：
10.1002/adbi.202200073
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发表时间：
2022-09
期刊：
影响因子：
3.7
通讯作者：
Albertson, Donna G.
中科院分区：
文献类型：
--
作者：
Dubeykovskaya, Zinaida A.;Tu, Nguyen Huu;Garcia, Paulina D. Ramirez;Schmidt, Brian L.;Albertson, Donna G.
口腔癌疼痛是由于癌症释放的介质，敏感和激活感觉神经元。足底注射人舌癌细胞系HSC-3或OSC-20的条件培养基（CM）引起伤害性行为。相比之下，来自非癌细胞系DOK和HaCaT的CM是非伤害感受性的。疼痛介质由癌细胞释放的细胞外囊泡（EV）携带。来自癌细胞系CM的EV的耗尽逆转机械异常性疼痛和热痛觉过敏。来自非伤害感受性细胞系的条件培养基在用HSC-3 EV重构时变得伤害感受性。我们鉴定了与HaCaT CM相比，在来自HSC-3和OSC-20 CM的EV中以增加的丰度存在的两种miRNA（hsa-miR-21- 5 p和hsa-miR-221- 3 p）。miRNA靶基因表明Toll样受体7（TLR 7）和8（TLR 8）通路以及通过白细胞介素6细胞因子家族信号转导受体（gp 130，由IL 6ST编码）和集落刺激因子受体（G-CSFR，由CSF 3R编码）、Janus激酶和信号转导和转录激活因子3（JAK/STAT 3）的信号传导可能参与口腔癌疼痛。这些研究证实了最近发现的癌症EV在疼痛中的作用，并增加了导致口腔癌疼痛的痛觉和镇痛癌症疼痛介质和途径的库。口腔癌患者在癌症部位遭受疼痛。口腔癌释放携带疼痛介质的细胞外囊泡（EV）。EV蛋白和miRNA货物可以通过直接的配体-受体相互作用或通过调节基因的表达或活性导致神经元中伤害感受性途径的活性增加或镇痛途径的活性降低而促成口腔癌疼痛。
Oral cancer pain is attributed to release from cancers of mediators that sensitize and activate sensory neurons. Intraplantar injection of conditioned media (CM) from human tongue cancer cell line HSC-3 or OSC-20 evokes nociceptive behavior. By contrast, CM from non-cancer cell lines, DOK and HaCaT are non-nociceptive. Pain mediators are carried by extracellular vesicles (EVs) released from cancer cells. Depletion of EVs from cancer cell line CM reverses mechanical allodynia and thermal hyperalgesia. Conditioned media from non-nociceptive cell lines become nociceptive when reconstituted with HSC-3 EVs. We identified two miRNAs (hsa-miR-21-5p and hsa-miR-221-3p) present in increased abundance in EVs from HSC-3 and OSC-20 CM compared to HaCaT CM. The miRNA target genes suggest potential involvement in oral cancer pain of the toll like receptor 7 (TLR7) and 8 (TLR8) pathways, as well as signaling through interleukin 6 cytokine family signal transducer receptor (gp130, encoded by IL6ST) and colony stimulating factor receptor (G-CSFR, encoded by CSF3R), Janus kinase and signal transducer and activator of transcription 3 (JAK/STAT3). These studies confirm the recent discovery of the role of cancer EVs in pain and add to the repertoire of algesic and analgesic cancer pain mediators and pathways that contribute to oral cancer pain. Oral cancer patients suffer pain at the site of the cancer. Oral cancers release extracellular vesicles (EVs) carrying pain mediators. The EV protein and miRNA cargoes can contribute to oral cancer pain by direct ligand-receptor interactions or by modulating expression or activity of genes leading to increased activity of nociceptive pathways or reduced activity of analgesic pathways in neurons.
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影响因子：
11.1
作者：
Bali, Kiran Kumar;Selvaraj, Deepitha;Satagopam, Venkata P.;Lu, Jianning;Schneider, Reinhard;Kuner, Rohini
通讯作者：
Kuner, Rohini
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DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
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通讯作者：
Croce, Carlo M.
影响因子：
4
作者：
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通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
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