Myoepithelial proteins that have important suppressive roles in breast cancer invasion

Parker lab projectMyoepithelial cells are spindle shaped cells that border the milk ducts of the breast and produce the basement membrane. It is the presence of these cells that distinguishes ductal carcinoma in situ (DCIS, an early cancer stage) from invasive carcinoma. The disruption of this boundary is required for the tumour cells to escape, from which they can spread throughout the breast and to other organs of the body. It has been hypothesised that the myoepithelial cells do not just provide a physical barrier but also express proteins that inhibit the outgrowth of the tumour.

Investigations in our laboratory have revealed a protease inhibitor that is expressed abundantly in the myoepithelial cells surrounding normal ducts. We hypothesise that expression of this inhibitor in the myoepithelial cells suppresses early tumour invasion through inhibition of pro-invasive proteases. Through the use of 3D culture assays we have been able to determine that myoepithelial cells can stop the invasive growth of cancer cells (pictured). These models will be used in the future to determine the role of specific proteins in inhibiting the outgrowth of early cancer lesions. Using clinical DCIS samples, we will analyse the immune landscape of early breast cancer and also validate such proteins as predictors of progression to invasive carcinoma.