中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2014年
1期
64-66
,共3页
雌激素%甲状腺癌%血管生成%血管内皮生长因子
雌激素%甲狀腺癌%血管生成%血管內皮生長因子
자격소%갑상선암%혈관생성%혈관내피생장인자
Estrogen%Thyroid cancer%Angiogenes%Vascular endothelial growth factor
目的 探讨雌激素在甲状腺癌肿瘤微环境中对内皮细胞的促血管生成作用以及与血管内皮生长因子(VEGF)受体的关系.方法 免疫荧光检测雌激素受体(ER)在甲状腺癌细胞中的表达;检测雌二醇(E2)在有/无其雌激素受体抑制剂氟维司群(fulvestrant)时,处理乳头状甲状腺癌细胞(BCPAP)以及滤泡性甲状腺癌细胞(ML-1)的培养基对人脐静脉细胞(HUVECs)管腔形成和迁移的影响,探讨E2对VEGF分泌的影响以及VEGF在雌激素作用于内皮细胞中的机制.结果 BCPAP细胞均有ERα和ERβ的表达;经E2处理的BCPAP细胞和ML-1细胞的培养基均可以诱导HUVECs管腔的形成,且在加入ER的拮抗剂后管腔形成降低;E2可以显著增加ML-1细胞VEGF的含量(40.1%),而在加入fulvestrant后其增加作用被抑制;在无VEGF中和性抗体的情况下,E2处理的BCPAP细胞和ML-1细胞的培养基均可以诱导HUVECs的迁移率升高25.6%和30.1%,也可以引起管腔形成,且这种作用可以被fulvestrant抑制.但是在有VEGF中和性抗体时,E2处理的BCPAP细胞和ML-1细胞的培养基均没有诱导,迁移率均为100%左右,也没有管腔形成的作用.结论 雌激素通过激活甲状腺癌细胞的ER使VEGF表达增加,从而加速内皮细胞的迁移和管腔形成.
目的 探討雌激素在甲狀腺癌腫瘤微環境中對內皮細胞的促血管生成作用以及與血管內皮生長因子(VEGF)受體的關繫.方法 免疫熒光檢測雌激素受體(ER)在甲狀腺癌細胞中的錶達;檢測雌二醇(E2)在有/無其雌激素受體抑製劑氟維司群(fulvestrant)時,處理乳頭狀甲狀腺癌細胞(BCPAP)以及濾泡性甲狀腺癌細胞(ML-1)的培養基對人臍靜脈細胞(HUVECs)管腔形成和遷移的影響,探討E2對VEGF分泌的影響以及VEGF在雌激素作用于內皮細胞中的機製.結果 BCPAP細胞均有ERα和ERβ的錶達;經E2處理的BCPAP細胞和ML-1細胞的培養基均可以誘導HUVECs管腔的形成,且在加入ER的拮抗劑後管腔形成降低;E2可以顯著增加ML-1細胞VEGF的含量(40.1%),而在加入fulvestrant後其增加作用被抑製;在無VEGF中和性抗體的情況下,E2處理的BCPAP細胞和ML-1細胞的培養基均可以誘導HUVECs的遷移率升高25.6%和30.1%,也可以引起管腔形成,且這種作用可以被fulvestrant抑製.但是在有VEGF中和性抗體時,E2處理的BCPAP細胞和ML-1細胞的培養基均沒有誘導,遷移率均為100%左右,也沒有管腔形成的作用.結論 雌激素通過激活甲狀腺癌細胞的ER使VEGF錶達增加,從而加速內皮細胞的遷移和管腔形成.
목적 탐토자격소재갑상선암종류미배경중대내피세포적촉혈관생성작용이급여혈관내피생장인자(VEGF)수체적관계.방법 면역형광검측자격소수체(ER)재갑상선암세포중적표체;검측자이순(E2)재유/무기자격소수체억제제불유사군(fulvestrant)시,처리유두상갑상선암세포(BCPAP)이급려포성갑상선암세포(ML-1)적배양기대인제정맥세포(HUVECs)관강형성화천이적영향,탐토E2대VEGF분비적영향이급VEGF재자격소작용우내피세포중적궤제.결과 BCPAP세포균유ERα화ERβ적표체;경E2처리적BCPAP세포화ML-1세포적배양기균가이유도HUVECs관강적형성,차재가입ER적길항제후관강형성강저;E2가이현저증가ML-1세포VEGF적함량(40.1%),이재가입fulvestrant후기증가작용피억제;재무VEGF중화성항체적정황하,E2처리적BCPAP세포화ML-1세포적배양기균가이유도HUVECs적천이솔승고25.6%화30.1%,야가이인기관강형성,차저충작용가이피fulvestrant억제.단시재유VEGF중화성항체시,E2처리적BCPAP세포화ML-1세포적배양기균몰유유도,천이솔균위100%좌우,야몰유관강형성적작용.결론 자격소통과격활갑상선암세포적ER사VEGF표체증가,종이가속내피세포적천이화관강형성.
Objective To explore the induction of a proangiogenic phenotype in endothelial cells in the thyroid tumor microenvironment by estrogen-treated thyroid cancer cells and to define the role of vascular endothelial growth factor (VEGF) in this interaction.Methods Immunofluorescence was used to detect the expression estrogen receptor (ER) in thyroid cancer cells.Thyroid tumor cell lines BCPAP (papillary thyroid cancer) and ML-1 (follicular thyroid cancer) were cultured with estradiol in the absence or presence of an ER inhibitor (fulvestrant) and the media were used to treat human umbilical vein endothelial cells (HUVECs).Conditioned medium was then used to evaluate the induction of HUVECs tubulogenesis and migration.Secretion of VEGF in this medium was evaluated by Western blotting analysis.The subsequent effects of an ER inhibitor (fulvestrant) and a neutralizing VEGF antibody were also observed.Results ERα and ERβ were expressed in thyroid cancer cells.Estrogen-stimulated ML-1 cells secreted an increased amount of VEGF near 40.1% likely as a result of ER signaling.In contact with this environment,HUVECs demonstrated enhanced tubulogenesis and migration of 25.6% and 30.1%.Western blotting analysis documented estrogen-mediated up-regudation of phosphoinositide 3-kinase (PI3K) in HUVECs.These effects were mitigated by an ER inhibitor (fulvestrant/ICI) and a neutralizing VEGF antibody.Conclusion Estrogen can induce a proangiogenic endothelial cell phenotype in the thyroid tumor microenvironment through ER and VEGF signaling.