HYAL1 overexpression is correlated with the malignant behavior of human breast cancer
HYAL1 overexpression is correlated with the malignant behavior of human breast cancer
复制标题
HYAL1过表达与人类乳腺癌恶性行为相关
DOI：
10.1002/ijc.25460
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发表时间：
2011-03-15
影响因子：
6.4
通讯作者：
Ren, Guo-Sheng
中科院分区：
文献类型：
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作者：
Tan, Jin-Xiang;Wang, Xiao-Yi;Ren, Guo-Sheng
细胞外基质（Extracellular matrix，ECM）与肿瘤细胞的生长、增殖、转移、血管生成等密切相关，透明质酸（hyaluronicacid，HA）是ECM的组成成分，透明质酸酶（hyaluronidase，HAase）是一种降解HA的内切糖苷酶。HAase的水平在许多癌症中升高。透明质酸酶-1（HYAL 1）是主要的肿瘤源性HA酶。本研究检测了HYAL 1在乳腺癌细胞和组织中的表达水平，并测定了乳腺癌细胞中HAase活性的量。与乳腺癌细胞系HBL-100和正常乳腺组织相比，HYAL 1在乳腺癌细胞系MDA-MB-231、MCF-7、浸润性导管癌组织和转移淋巴结中均过表达。因此，MDA-MB-231和MCF-7中的HAase活性量高于HBL-100中的HAase活性量。此外，MDA-MB-231和MCF-7细胞中HYAL 1表达的敲低导致细胞生长、粘附、侵袭和血管生成潜能的降低。同时，HYAL 1基因敲低显著抑制乳腺癌细胞异种移植瘤生长和微血管密度。进一步的研究表明，乳腺癌组织中HYAL 1、HYAL 2和HA的表达均升高，且HYAL 1可下调HA的表达。结论：HYAL 1可能是乳腺癌潜在的预后标志物和治疗靶点。
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.