Physiological Reviews, Vol 76, 69-125, Copyright © 1996 by American Physiological Society
Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction
L. Ronnov-Jessen, O. W. Petersen and M. J. Bissell
Structural Cell Biology Unit, Panum Institute, University of Copenhagen, Denmark.
Reciprocal interactions between epithelium and mesenchyme mediate crucial
aspects of embryonic development and direct the coordinated organogenesis,
correct spatial orientation, and the timely expression of functional
activity consistent with physiological demands. The mesenchymal equivalent
in the adult organism is the stroma, i.e., the loose connective tissue that
is separated from the epithelial compartment by an intact basement
membrane. In carcinomas, the cellular organization is dramatically changed,
and the stroma is extensively modified. The basement membrane is penetrated
in a process of degradation and/or decreased synthesis, and direct contact
between tumor cells and the surrounding stroma coincides with
neovascularization, inflammatory cell influx, and extensive remodeling of
extracellular matrix. In this review, we highlight our current knowledge of
tumor cell stromal interactions in the mammary gland with particular
emphasis on cellular origins and functional phenotypes. We focus both on
normal mammary gland and breast tumors and on culture systems developed to
dissect individual aspects of cell-cell and cell-extracellular matrix
interactions.
