Tumour-stromal interactions: Integrins and cell adhesions as modulators of mammary cell survival and transformation

Homeostasis in the mammary gland is achieved by a balance between cell proliferation and cell death (apoptosis), which is reflected by an organized tissue structure. Breast cancer, which is a loss of tissue homeostasis, is characterized by perturbations in mammary tissue architecture, that is linked to alterations in the extracellular matrix (ECM) and in the adhesion molecules expressed by the MECs [1]. Correcting the adhesion defects in the mammary tumor epithelia can restore tissue organization and normal behavior to some breast tumor cells [2]. Conversely, altering the stromal microenvironment of the breast promotes the expression of tumorigenic potential in MECs [3]. This suggests that aspects of the breast cancer phenotype arise from alterations in the dynamic interplay between the epithelial cells, the mammary stroma, and the structural organization of the breast. Gaining an understanding of how disturbances in this relationship relate to the pathogenesis of human breast cancer will depend on delineating the subtleties of this dialog. This will require the application of appropriate model systems that can reconstitute stromal–epithelial interactions in the context of a three-dimensional tissue structure.Breast cancers typically exhibit low rates of cell proliferation (apoptosis deregulation), often recur after years of dormancy (apoptosis evasion), and once re-established frequently acquire resistance to treatment (apoptosis resistance). As such, alterations in apoptosis probably predominate in the pathogenesis of human breast cancer. Therefore, an understanding of how the stroma influences adhesion and tissue architecture to modulate MEC survival, and how these pathways become deregulated in mammary tumors, should help to define the critical events that regulate breast cancer pathogenesis. In the present brief review, we discuss how altered stromal–epithelial interactions and changes in cell adhesion and tissue architecture influence MEC survival to drive mal