INSULIN-LIKE GROWTH-FACTOR MEDIATED STROMAL-EPITHELIAL INTERACTIONS IN HUMAN BREAST-CANCER

The prominent 'desmoplastic' or stromal reaction seen in many invasive breast carcinomas lead to early speculation that stromal cells play a role in breast cancer pathogenesis [1]. Experimental evidence now sup ports this hypothesis and interactions between stromal cells and epith elial cells appear to be important for both normal mammary development and neoplasia. The identification of genes that are selectively expre ssed in the stroma of malignant breast lesions has recently provided n ew insights into the molecular basis of stromal-epithelial interaction s. Stromally expressed genes include growth factors, proteases and ext racellular matrix proteins, all biological activities with potential r oles in malignant progression. Investigations discussed here concern t he nature of the paracrine signals provided by malignant epithelial ce lls that activate changes in stromal gene expression, the effect that the stromally derived factors have on the behavior of malignant epithe lial cells and the identification of novel factors and receptors in ei ther stroma or epithelia that contribute to their mutual interactions. These questions will be addressed in the context of this laboratory's studies on insulin-like growth factors, as these molecules show marke d differences in stromal expression between benign and malignant breas t tissue and thus provide a useful paradigm for investigations into th e paracrine environment of an evolving breast tumor.