The Role of Heparanase in the Invasion and Metastasis of Breast Carcinoma and Its Regulation Mechanism
10.3969/j.issn.1000-8179.2010.05.017
- VernacularTitle:乙酰肝素酶在乳腺癌侵袭转移中的作用及调控机制
- Author:
Linde LI
;
Junqiang CHEN
- Publication Type:Journal Article
- Keywords:
Heparanase;
Breast carcinoma;
Invasion and metastasis;
Regulation mechanism
- From:
Chinese Journal of Clinical Oncology
2010;37(5):293-296
- CountryChina
- Language:Chinese
-
Abstract:
Heparanase is the only one endogenous glucuronidase found in mammalian cells up to now,and can degrade the heparan sulfate which is the side chain of heparin sulfate proteoglycans existing in the extracellular matrix and basement membrane.Heparanase is considered as an ideal target for the treatment of cancer metastasis.High expression of heparanase gene was found in breast cancer,and was closely associated with tumor size and lymph node metastasis.In vitro,high level of heparanase promoter activity was found in breast cancer cells.In vivo,compared with negative control group,breast cancer cells transfected with heparanase could generate higher tumor volume,tumor weight,microvessel density and longer survival time of cancer cells.Blockage or silencing of heparanase gene expression through antisense technology or RNA interference technology could reduce the ability of adhesion and invasion of breast cancer cells,indicating that heparanase played important roles in the invasion and metastasis of breast cancer.Mechanisms involved in the regulation of heparanase in the invasion and metastasis of breast cancer are as following.Estrogen could bind to its recaptor and then affect the specific region of heparanase gene which could activate heparanase transcription and the expression of hepamnase Mrna and protein.Heparanase could increase the secretion of osteoclast-stimulating factor which could cause the osteolytic lesions in the absence of detectable bone metastasis.Heparanase could also induce circulating lymphocytes to produce stimulating factors which might promote the invasion and metastasis of breast cancer.Furthermore,p53 gene,ETS gene,EGR1 gene,PI-88 factor,and Cox-2 could also regulate the expression of heparanase gene.This article reviewed the role of heparanase in the invasion and metastasis of breast cancer and summarized the corresponding regulation mechanisms.
