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

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.Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM. It is a nonsulfated glycosaminoglycan made up of repeating disaccharide units, D-glucuronic acid and N-acetyl-D-glucosamine. HA keeps tissues hydrated and maintains osmotic balance and cartilage integrity.

Evidence of epigenetic regulation of the tumor suppressor gene cluster flankingRASSF1in breast cancer cell lines

“…HAase levels were demonstrated to be elevated in breast tumors, and RT-PCR analysis has detected the expression of HYAL2 and HYAL3 in breast cancer tissues, 34 suggesting an association between HAase and the tumor invasive/metastatic phenotype. 35,36 In accordance with the data from the present study demonstrating higher levels of HYAL2 in breast cancer cell lines compared with nontumorigenic cell line 184A1, previous reports have shown that, whereas less invasive breast cancer cells expressed HYAL3, highly invasive cells expressed HYAL2. 34 Although the promoter region of these genes is characterized by a CpG island, their expression levels were not significantly increased after the treatments with the demethylating agents in our study.…”

Hyaluronan Associated Inflammation and Microenvironment Remodelling Influences Breast Cancer Progression

“…In BCA, HYAL-1 and HYAL-2 are often coordinately overexpressed compared to non-malignant breast tissue. Knockdown of HYAL-1, which is overexpressed in MDA-MB-231 and MCF-7 BCA lines, reduces tumour xenograft size (Tan et al, 2010). 3. HA receptors detect oligosaccharides and fragments: Control of key signalling pathways by HA fragments 3.1 CD44 CD44 is a class I transmembrane receptor, which binds to HA via a link domain and is expressed by a variety of cells, including fibroblasts, endothelial and epithelial cells, smooth muscle, and haematopoietic cells.…”

“…In general, high MW HA inhibits angiogenesis while fragments promote angiogenesis. Overexpression of HA and HYALs has been linked to an increase in angiogenesis in several types of cancers including breast (Tan et al, 2010), bladder (Lokeshwar et al, 2000, Golshani et al, 2008, prostate (Ekici et al, 2004, Bharadwaj et al, 2007, and endometrial (Paiva et al, 2005). Koyama et al (2007) demonstrated that an increase in HAS2 expression by genetic modifications in a mouse model of BCA causes a higher incidence of adenocarcinoma accompanied by an increase in angiogenesis (Koyama et al, 2007).…”

Analyzing the Role of Spectral Indices in Differentiating Benign and Malignant Breast Lesions

“…There is a complex interrelationship among angiogenesis, hyaluronic acid, and certain enzymes, 3 Presence of higher-than normal amounts of hyaluronic acid facilitates the growth and spread of the tumor in several ways. It is extremely hydrated, facilitating the passage of nutrients into and wastes from tumor cells until the tumor reaches the critical size at which passive diffusion is no longer enough.…”