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乙酰肝素酶(Heparanase,HPSE)是目前发现的哺乳动物细胞中唯一能降解细胞外基质和基底膜中硫酸肝素蛋白多糖侧链—硫酸乙酰肝素的内源性糖苷酶,是目前抗肿瘤转移的理想靶点。HPSE在乳腺癌中常有高表达,并与肿瘤大小和淋巴结转移等密切相关。体外研究表明,乳腺癌细胞中HPSE启动子活性增高,转染HPSE的乳腺癌细胞在体内成瘤后,其肿瘤体积、重量、微血管密度以及癌细胞存活时间均明显高于阴性对照组。应用反义核酸技术或RNA干扰技术封闭或沉默HPSE基因表达后,乳腺癌细胞黏附和侵袭能力显著降低,表明HPSE在乳腺癌侵袭转移中发挥极其重要的作用。HPSE在乳腺癌侵袭转移中受多种机制调控,主要有:雌激素与其受体结合后作用于HPSE基因特定区域,从而提高HPSE转录活性,增强其基因和蛋白的表达:HPSE可使破骨细胞刺激因子产生增加,从而导致骨质溶解破坏,为乳腺癌骨转移奠定基础;HPSE诱导循环淋巴细胞产生刺激因子,从而促进乳腺癌的侵袭转移。此外,HPSE基因还受p53基因、ETS基因、EGR1基因、PI-88因子、COX-2等的调控。本文就HPSE在乳腺癌中的表达状况、在侵袭转移中的作用及调控机制进行综述。
Heparanase (HPSE) is the only endogenous glycosidase in mammalian cells that can degrade the heparin sulfate proteoglycan side chain-heparan sulfate in the extracellular matrix and basement membrane. It is currently the anti-tumor metastasis Ideal target. HPSE is often highly expressed in breast cancer and is closely related to tumor size and lymph node metastasis. In vitro studies showed that the activity of HPSE promoter in breast cancer cells was increased. The tumor volume, weight, microvessel density and survival time of cancer cells in HPSE-transfected breast cancer cells were significantly higher than those in the negative control group after in vivo tumorigenesis. The ability of blocking or silencing HPSE gene expression using antisense or RNAi technology significantly reduced the ability of breast cancer cells to adhere and attack, indicating that HPSE plays an extremely important role in the invasion and metastasis of breast cancer. HPSE is regulated by many mechanisms in the invasion and metastasis of breast cancer. Estrogen binds to its receptor and then acts on a specific region of HPSE gene to enhance the transcriptional activity of HPSE and enhance its gene and protein expression. HPSE can make osteoclast Stimulation factor increased, leading to destruction of osteoporosis, breast cancer bone metastasis lay the foundation; HPSE induced by circulating lymphocytes to stimulate factors, thereby promoting the invasion and metastasis of breast cancer. In addition, HPSE gene is regulated by p53 gene, ETS gene, EGR1 gene, PI-88 factor and COX-2. In this paper, the expression of HPSE in breast cancer, the role of invasion and metastasis and regulatory mechanisms are reviewed.