EFEMP1对卵巢癌细胞侵袭转移和血管生成作用的研究

Peritoneal dissemination and distant metastasis of ovarian cancer is the most important cause of high mortality. To clarify the mechanism of ovarian cancer metastasis to facilitate the early diagnosis and prevention will be the key to improve the treatment effect of ovarian cancer. In our previous study, using cDNA microarray, we analyzed the gene different expressions between the high invasive subclone and the low invasive subclone, the results suggest that EFEMP1 may be associated with ovarian cancer invasion and metastasis. Further RNA interference experiments indicate that EFEMP1 promote ovarian cancer growth, invasion and mobility. Till now, the related reports about the role of EFEMP1 in ovarian cancer invasion, metastasis and angiogenesis have not been found at home and abroad. Using clinical specimens, we will further study the role of EFEMP1 in ovarian cancer development and angiogenesis, and then build visual orthotopic tumor model and ascites tumor model to mimic ovarian cancer growth and metastasis in vivo. Using PCR chip technology, we will deeply explore the mechanism of EFEMP1 in affecting ovarian cancer invasion, metastasis and angiogenesis and the downstream target genes of EFEMP1 during this process. Related results will provide theoretical basis for the prognosis estimate of ovarian cancer patients and the treatment of inhibition ovarian cancer invasion and metastasis.

卵巢癌的腹腔播散和远处转移是疾病致死的最重要原因，阐明卵巢癌转移的发生机制并对其进行及早的诊断和预防将是进一步提高卵巢癌治疗效果的关键所在。我们在前期的研究中利用基因芯片对不同转移能力的克隆细胞株的基因表达差异进行分析，结果提示EFEMP1可能与卵巢癌的侵袭转移密切相关。进一步的RNA干扰实验结果显示EFEMP1促进卵巢癌的生长、侵袭和移动。目前关于EFEMP1对卵巢癌细胞侵袭转移和血管生成作用的研究国内外尚未见相关报道。本课题将进一步从临床标本中检测EFEMP1对卵巢癌发生发展和血管生成的作用，同时建立可视裸鼠原位移植瘤模型和腹水瘤模型，在体内模拟卵巢癌生长、侵袭和转移的过程，并利用PCR芯片技术，深入探讨EFEMP1在影响卵巢癌细胞侵袭转移过程中和血管生成过程中的作用机制及其调控的下游靶基因，相关结果将为卵巢癌患者的的预后判断和针对抑制侵袭性的卵巢癌的治疗提供理论基础

卵巢癌的腹腔播散和远处转移是疾病致死的最重要原因，阐明卵巢癌转移的发生机制并对其进行及早的诊断和预防将是进一步提高卵巢癌治疗效果的关键所在。我们在前期的研究中利用基因芯片对不同转移能力的克隆细胞株的基因表达差异进行分析，结果显示EFEMP1在高转移克隆细胞株S1中呈现高表达，而在低转移克隆细胞株S21中呈现低表达，提示EFEMP1可能与卵巢癌的侵袭转移密切相关。为进一步明确EFEMP1在卵巢癌侵袭转移中的作用机制，我们利用慢病毒介导的方式外源性强制EFEMP1在低转移克隆细胞株S21中的表达，同时RNA干扰抑制EFEMP1在高转移克隆细胞株S1中表达，并进行生长曲线、软琼脂培养克隆形成实验、流式细胞仪检测细胞周期和裸鼠体内成瘤试验，结果提示EFEMP1促进卵巢癌细胞的增值、侵袭和转移，进一步信号通路研究显示EFEMP1可以激活PI3K/AKT通路，上皮-间质 PCR 芯片结果显示，EFEMP1可以促进卵巢癌细胞的上皮间质转换。临床标本检测发现，卵巢癌组织中EFEMP1高表达，并与临床分期、分化程度、有无淋巴结转移和患者预后密切相关。总之，EFEMP1与卵巢癌发生发展及侵袭转移密切相关，为卵巢癌的治疗提供新的思路。