Model depicting the role of the microenvironment in suppressing or promoting the tumor cell metastatic phenotype. Current data suggest that the microenvironment can suppress a malignant cell from forming an aggressive tumor. Similarly, early-stage lesions can be promoted by a microenvironment that is either permissive or instructive for metastasis. Thus, the stroma is identified as an important target for preventive and therapeutic drug development.

Ductal carcinoma of the breast surrounded by a fibrous stromal sheath. Depicted is a single duct containing an intraductal carcinoma. White arrows show lumen-like structures; however, normal epithelial cell polarity is lost. Black arrows show delineation between tumorigenic mammary epithelial cells and stromal tissue. The asterisk shows stromal sheath encapsulating the ductal carcinoma in situ. Magnification: 400×. From University of Connecticut's Virtual Pathology Museum .

Human mammary epithelial MCF12A cells stably transfected with oncogenic V12Ras exhibit a functional epithelial-to-mesenchymal transition, which is consistent with a metastatic phenotype. (a) Diagram of normal mammary epithelial cell with extensive cell–cell junctional complexes, apical–basal polarity, and apical secretion. (b) Diagram of mesenchymal-like cell with lack of cell–cell junctions and front to back polarity typical of a motile cell. (c) Immortalized but non-tumorigenic MCF12A cells form a duct-like structure in three-dimensional culture with polarized cells that have extensive cell–cell interactions – attributes of normal mammary epithelial cells in vivo, ×400. (d) MCF12A cells transfected with oncogenic Ras show characteristics of metastatic cells in three-dimensional culture, with loss of cell–cell interactions and gain of front–back polarity, which are hallmarks of the mesenchymal cell, ×400. BM, basement membrane; GJ, gap junction; JC, junctional complex; ME, myoepithelial cell; MFG, mammary fat globule.