Role of myoepithelial cells in breast tumor progression

Abstract

Myoepithelial cells form a semi-continuous protective sheet separating the human breast epithelium and the surrounding stroma. They suppress stromal invasion of tumor cells by the secretion of various anti-angiogenic and anti-invasive factors. The disruption of this cell layer results in the release of the growth factors, angiogenic factors, and reactive oxygen species causing an alteration in the microenvironment. This helps in the proliferation of surrounding cells and increases the invasiveness of tumor cells. Two theories are proposed for the mechanism of tumor epithelial cells progression from in situ to invasive stage. According to the first theory, tumor cell invasion is triggered by the overproduction of proteolytic enzymes by myoepithelial cells and surrounding tumor cells. The second theory states that tumor invasion is a multistep process, the interactions between damaged myoepithelial cells and the immunoreactive cells trigger the release of basement membrane degrading enzymes causing tumor progression. Further studies in understanding of molecular mechanism of myoepithelial cell functions in tumor suppression may lead to the identification of novel therapeutic targets for breast cancer.

Figure 1

Cross section of a normal mammary gland duct.

Figure 2

Structural relationship between mammary gland duct cells, BM and stroma.

Figure 3

Degradation of the BM resulting in the stromal invasion by tumor cells. (i). Myoepithelial cells are damaged by various factors releasing the inner contents like the diffusible molecules and chemoattractants. (ii). Immunoreactive cells (IRC) attracted to the luminal space by these chemoattractants. (iii). IRCs activated by coming in contact with chemoattractants and secrete different proteolytic enzymes (iv). These proteolytic enzymes then degrade the basement membrane resulting in gaps. (v). Tumor cells enter the stromal region through these gaps.