Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation

Tumors arise from cells that have sustained genetic mutations resulting in deregulation of several of their normal growth-controlling mechanisms. Much of the research concerning the origins of cancer has focused on the geneti c mutations within tumor cells, treating tumorigenesis as a cell-autonomous process governed by the genes carried by the tumor cells themselves. Howev er, it is increasingly apparent that the stromal microenvironment in which the tumor cells develop profoundly influences many steps of tumor progressi on. In various experimental tumor models, the microenvironment affects the efficiency of tumor formation, the rate of tumor growth, the extent of inva siveness, and the ability of tumor cells to metastasize. In carcinomas, the influences of the microenvironment are mediated, in large part, by paracri ne signaling between epithelial tumor cells and neighboring stromal fibrobl asts, In this review, we summarize recent advances in understanding the par acrine signaling interactions between epithelial cancer cells and associate d fibroblasts and examine the effects of these bidirectional interactions o n various aspects of carcinoma formation. We note, however, that paracrine signaling between other cell types within the carcinomas, such as endotheli al cells and inflammatory cells, may play equally important roles in tumor formation and we will refer to these heterotypic interactions where relevan t. (C) 2001 Academic Press.