Proteinases in breast cancer progression

Attenuation of the malignant phenotype of breast cancer cells upon treatment with a serine proteinase inhibitor.

When cultured in 3D laminin-rich gels, normal breast epithelial cells form growth-arrested, spherical cellular structures with apicobasal polarity that are reminiscent of normal mammary acini, while breast-derived cancer cells, cultured under the same conditions, continue to proliferate into amorphous masses. This 3D culture system provides a useful tool to study cell-cell and cell-microenvironment interactions, how these interactions are involved in and affected by cancer progression, and the roles played by proteinases in these processes.

We have observed that treatment of malignant breast cells in 3D culture with certain inhibitors of serine proteinases suppresses the malignant phenotype, causing cancer cells to develop into organized structures more typical of normal cells (see figure). We are working to identify the serine proteinase(s) for which specific inhibition in this culture assay results in suppression of the malignant phenotype, with the rationale that such malignancy-promoting enzymes may represent novel and promising targets for breast cancer therapy.