Alterations in tissue structure and loss of coordinated growth and adhesion in breast cancer

Breast cancer is characterized by growth autonomy, anchorage-independent survival and loss of breast-specific tissue structure. Using a novel breast tumor cell series we have recently demonstrated that alterations in cell- extracellular matrix interactions, via integrins, are critical determinants of the mammary epithelial cell (MEC) phenotype and can dominantly modulate their growth and survival. We have now determined that there exists a dynamic reciprocal modulation between growth receptor and integrin pathways which is dependent upon MEC tissue structure and drives MEC morphogenesis. Using our tumor progression series we have additionally found that loss of tissue structure and coordinated growth and adhesion precede and may be critical for malignant transformation. Studies are now underway to understand the mechanistic basis for this structurally driven coordinated regulation.