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透明质酸酶 1 过表达与人乳腺癌的恶性行为相关。

HYAL1 overexpression is correlated with the malignant behavior of human breast cancer.

机构信息

Department of Endocrine Surgery, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

出版信息

Int J Cancer. 2011 Mar 15;128(6):1303-15. doi: 10.1002/ijc.25460.

Abstract

Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM, and hyaluronidase (HAase) is a HA-degrading endoglycosidase. Levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. In this study, we detected HYAL1 expression levels in breast cancer cells and tissues, and measured the amount HAase activity in breast cancer cells. Compared with nonmalignant breast cell line HBL-100 and normal breast tissues, HYAL1 were overexpressed in breast cancer cell lines MDA-MB-231, MCF-7, invasive duct cancer tissues and metastatic lymph nodes, respectively. Accordingly, the amount HAase activity in MDA-MB-231 and MCF-7 was higher than that in HBL-100. In addition, knockdown of HYAL1 expression in MDA-MB-231 and MCF-7 cells resulted in decreased cell growth, adhesion, invasion and angiogenesis potential. Meantime, the HYAL1 knockdown markedly inhibited breast cancer cell xenograft tumor growth and microvessel density. Further studies showed that the HYAL1, HYAL2 and HA were elevated in breast cancer, and HYAL1 could downregulate HA expression. In conclusion, HYAL1 may be a potential prognostic marker and therapeutic target in breast cancer.

摘要

细胞外基质 (ECM) 与肿瘤细胞的生长、增殖、转移和血管生成等密切相关。透明质酸 (HA) 是 ECM 的组成部分,而透明质酸酶 (HAase) 是一种 HA 降解的内切糖苷酶。许多癌症中 HAase 的水平升高。透明质酸酶-1 (HYAL1) 是主要的肿瘤源性 HAase。在本研究中,我们检测了乳腺癌细胞和组织中的 HYAL1 表达水平,并测量了乳腺癌细胞中 HAase 活性的量。与非恶性乳腺细胞系 HBL-100 和正常乳腺组织相比,乳腺癌细胞系 MDA-MB-231、MCF-7、浸润性导管癌组织和转移性淋巴结中分别过表达 HYAL1。相应地,MDA-MB-231 和 MCF-7 中的 HAase 活性高于 HBL-100。此外,MDA-MB-231 和 MCF-7 细胞中 HYAL1 表达的敲低导致细胞生长、黏附、侵袭和血管生成潜力降低。同时,HYAL1 的敲低显著抑制了乳腺癌细胞异种移植肿瘤的生长和微血管密度。进一步的研究表明,乳腺癌中 HYAL1、HYAL2 和 HA 升高,而 HYAL1 可以下调 HA 的表达。总之,HYAL1 可能是乳腺癌的一个有潜力的预后标志物和治疗靶点。

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