Untitled

Abstract

We used enzymatic activity and immunochemical quantifications to analyse the expression and secretion of cathepsin D by human breast cancer cell lines of different invasive potentials (MCF-7/6, MCF-7/AZ, MDA-MB-231). This study does not directly prove that cathepsin D or procathepsin D is involved in human breast cancer cell invasion and metastasis but it shows that the proportion of procathepsin D (activity and antigen) secreted by the human breast cancer cell lines tested correlates with their invasive potential. In the estrogen receptor-positive MCF-7 subclones, this proportion is increased by estradiol only in the invasive MCF-7/6 variant. The cell content in procathepsin D is increased by estrogens to a greater extent in MCF-7/6 cells as compared to non-invasive MCF-7/AZ cells. Tamoxifen appears to be an estrogen agonist concerning cathepsin D regulation, whereas ICI 182,780 is a true antagonist. Our results suggest that synthesis and secretion of cathepsin D are regulated at two distinct levels and differentially affected by estrogens. Synthesis only seems to be affected in non-invasive MCF-7/AZ cells, whereas in invasive MCF-7/6 cells, both synthesis and the efficiency of secretion are increased by estrogens. Our results also confirm that the key site of regulation leading to lysosomal enzyme oversecretion is the Golgi apparatus insulin-like growth factor-II/mannose 6-phosphate receptor.

Procathepsin D expression correlates with invasive and metastatic phenotype of MDA-MB-231 derived cell lines

“…Interestingly, the increased invasion directly coincided with the level of secreted pCD in these cell lines. This result is consistent with the earlier study [20] as well as that of ours [21], showing a direct relationship between pCD secretion and invasive potential of different breast cancer cell lines. In addition, treatment of cells with synthetic AP resulted in enhanced invasion as compared to their respective controls and the effect could be reversed by anti-AP antibodies showing that the effect was through AP as earlier reported in the case of ZR-75-1 cells and MCF-7 cells [22].…”

“…Couissi et al has reported that the proportion of pCD secreted by the human breast cancer cell lines correlates with their invasive potential [20]. Therefore, these three cell lines with varying levels of secreted pCD were analyzed for their invasive potential using an in vitro Matrigel coated membrane.…”