Effects of hyaluronan on the invasive properties of human breast cancer cells in vitro

Abstract

Hyaluronan (HA) is a high molecular weight glycosaminoglycan present mostly in the extracellular matrix (ECM). HA binds to specific receptors such as CD44. Its production is increased at the tumour-stroma interface, including those in breast cancer tumours. It has been suggested that it facilitates invasion of tumour cells into the ECM by a hydrodynamic effect, or by altering tumour cell behaviour. Using in vitro tests we studied the effect of immobilized (iHA) and soluble (sHA) HA on the invasive properties of four human breast cancer cell lines with different levels of CD44 expression. Our results show that iHA acts as an adhesive, haptotactic, and motility stimulating factor for the CD44 positive Hs578T cells and induces the expression of membrane CD44. sHA also changes the motility properties of the Hs578T and MDA-231 cells and increases their CD44 expression. sHA or iHA have no measurable effect on the adhesion, motility or CD44 expression of the ZR-75-1 and MCF-7 breast cancer cells. Our results establish that in high CD44 expressing breast cancer cells HA modulates tumour cell adhesion and motility and also increases the expression of its own receptor, CD44.

Polypyrrole Nanospheres with Magnetic and Cell‐Targeting Capabilities

“…The observed uptake of NS(HA) could be a result of non‐specific binding to the cells. Non‐specific binding may have resulted from the cell‐adhesion promoting property of HA, which has been implicated in cancer cell adhesion 21,22. When the cells were incubated with NS(HA)‐HER, a greater than seven‐fold increase in iron uptake [as compared to that for NS(HA)] was observed (59.5 ± 1.0 pg · cell −1 at 2 h and 197.5 ± 17.0 pg · cell −1 at 24 h).…”

Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells

“…Although mice lacking CD44 developed a similar incidence of primary tumors in response to the APC or p53 gene mutations as the CD44 expressing mice, knocking out CD44 resulted in a complete inability of these mice to develop metastatic lesions (Weber et al, 2002). In vitro studies have also demonstrated that HA promotes the invasion of breast cancer cells through experimental extracellular matrices as a consequence of activating CD44 (Herrera-Gayol and Jothy, 2001). Our laboratory has also recently established a role for CD44 expression in breast and prostate cancer cells in promoting their preferential adhesion to bone marrow endothelial cells (Draffin et al, 2004).…”

Efficient Cellular Labeling by CD44 Receptor‐Mediated Uptake of Cationic Liposomes Functionalized with Hyaluronic Acid and Loaded with MRI Contrast Agents

“…The capacity of these HA–L adducts in targeting CD44 receptors was explored with three tumor cell types (C6 rat glioma, B16‐F10 mice melanoma, and MCF7 human breast cancer) that have varied CD44 receptor expression levels 16. 22, 23 Cells (∼1.5×10 6 ) were incubated in medium containing HA–L (HA/liposome=4:1, the ratio of which is defined by moles of negative/positive charge), or nonfunctionalized Gd‐loaded liposomes (L) for 30 min. In both experiments the Gd concentration in the incubation medium was 0.01 m M .…”