| 曹宸,杨莹,孙秋悦,等.黑色素瘤细胞外泌体通过 Prospero同源异形盒蛋白 1调控肿瘤淋巴转移机制的研究[J].安徽医药,2023,27(7):1331-1337. |
| 黑色素瘤细胞外泌体通过 Prospero同源异形盒蛋白 1调控肿瘤淋巴转移机制的研究 |
| Study on the mechanism of melanoma cell exosomes regulating tumor lymphatic metastasis through Prox-1 |
| |
| DOI：10.3969/j.issn.1009-6469.2023.07.012 |
| 中文关键词: 黑色素瘤 外泌体 Prospero同源异形盒蛋白 1 微淋巴管密度 淋巴管内皮细胞透明质酸受体 -1 淋巴转移 |
| 英文关键词: Melanoma Exosomes Prospero homeobox protein 1(Prox-1) Microlymphatic vessel density Lymphatic vessel endothelial hyaluronic acid receptor-1(LYVE-1) Lymphatic metastasis |
| 基金项目:国家自然科学基金项目( 81641174)；江苏省卫生厅，江苏省青年医学人才项目( QNRC2016841)；江苏大学附属医院博士人才启动基金项目( jdfyRC2020001) |
|
| 摘要点击次数: 1921 |
| 全文下载次数: 723 |
| 中文摘要: |
| 目的探讨黑色素瘤外泌体( melanoma exosomes，MM-ex)携带的果蝇 Prospero同源异形盒蛋白 1(prospero homeobox protein 1，Prox-1)，在调控淋巴管内皮细胞(lymphatic endothelial cells，LECs)增殖、迁移以及生成具有转移肿瘤细胞功能淋巴管过程中的作用。方法采用慢病毒转染实验构建低表达 Prox-1黑色素瘤细胞株( MMshProx-1)。采用试剂盒法获取 MM和 MM-exshProx-1的外泌体( MM-ex和 MM-exshProx-1)。采用免疫荧光检测、蛋白质印迹法检测、细胞增殖及细胞迁移实验，观察 MM-ex及 MMexshProx-1对 LECs生物学特性的影响。采用免疫组化( IHC)法检测 2015年 9月至 2021年 4月江苏大学附属医院收治的 32例皮肤黑色素瘤病理标本中 Prox-1及淋巴管内皮细胞透明质酸受体 -1(lymphatic vessel endothelial hyaluronic acid receptor-1，LYVE-1)的表达情况，统计微淋巴管密度( microlymphatic vessel density，MLVD)并分析 Prox-1及 MLVD与黑色素瘤生物学特性的相关性。结果细胞实验: MM-ex促进淋巴管内皮细胞增殖及迁移，促进了淋，巴管的成形。 MM-exshProx-1对 LECs无增殖及迁移的影响，对淋巴管成形无促进作用。临床研究:免疫组化的结果表明 Prox-1、LYVE-1在黑色素瘤组织及肿瘤周围组织中的阳性表达率显著高于正常皮肤组织。 Prox-1信号在黑色素瘤淋巴结转移组和 Ⅲ期及 Ⅳ期肿瘤组的表达率［ 87.50%(14/16)、 79.17%(19/24)］明显高于无淋巴结转移组和 Ⅰ期及 Ⅱ期肿瘤组［ 37.50%(6/16)、 12.50%(1/8)］(均 P<0.05)。 LYVE-1在黑色素瘤转移组和 Ⅲ期及 Ⅳ期肿瘤组的表达( 9.30±4.65、5.15±1.72)明显高于无淋巴结转移组和 Ⅰ期及 Ⅱ期肿瘤组( 5.66±1.69、5.30±1.65，均 P<0.05)。 Prox-1、LYVE-1的表达情况均与病人的年龄、性别无关(均 P>0.05)。结论 MM-ex通过 Prox-1促进 LECs的增殖及迁移，在肿瘤淋巴管再生中起到重要作用。 Prox-1、LYVE-1及 MLVD与黑色素瘤淋巴转移及预后呈明显相关性，为皮肤黑色素瘤的早期淋巴转移及预后提供一个新的判断指标，也为皮肤黑色素瘤的临床治疗提供新的方法和策略。 |
| 英文摘要: |
| Objective To investigate the role of Prospero homeobox protein1(Prox-1) carried by melanoma exosomes (MM-ex) in regulating the proliferation, migration and formation of lymphatic endothelial cells (LECs).Methods The melanoma cell line with low expression of Prox-1 (MMshProx-1) was constructed by lentivirus transfection experiment. The exosomes of MM and MM-exshProx-1 (MM-ex and MM-exshProx-1) were obtained by kit method. The effects of MM-ex and MM-exshProx-1 on the biological characteristics of LECs were observed by immunofluorescence, Western blot, cell proliferation and cell migration. Immunohistochemical (IHC) method was used to detect the expression of Prox-1 and LYVE-1 in the pathological specimens of 32 patients with cutaneous melanoma treated in the Affiliated Hospital of Jiangsu University from September 2015 to April 2021, the microlymphatic vessel density (MLVD)was counted, and thecorrelation between Prox-1 and MLVD and the biological characteristics of melanoma was analyzed.Results Cell experiment: MM-ex promoted the proliferation and migration of lymphatic endothelial cells and the formation of lymphatic vessels. MM-exshProx-1 had no effect on the proliferation and migration of LECs, and had no effect on lymphangioplasty. Clinical study: the expression rate of Prox-1 signal in melanoma lymph node metastasis group and advanced tumor [87.50%(14/16),79.17%(19/24)] was significantly higher than thatin non-lymph node metastasis group and early tumor group [37.50%(6/16),12.50%(1/8), P<0.05]. The expression of LYVE-1 in melanoma metastasis group and advanced cancer group (9.30±4.65, 5.15±1.72, P<0.05) was significantly higher than that in non-lymph node metastasis group and early cancer group (5.66±1.69, 5.30±1.65, P<0.05). The expressions of Prox-1 and LYVE-1 were not related to the age and gender of patients (P>0.05).Conclusions MM-ex promotes the proliferation and migration of LECs through Prox-1 and plays an important role in tumor lymphatic regeneration. Prox-1, LYVE-1 and MLVD are significantly correlated with the lymphatic metastasis and prognosis of melanoma, which not only provides a new judgment index for the early lymphatic metastasis and prognosis ofskin melanoma, but also provides a new method and strategy for the clinical treatment of skin melanoma. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
