Loch-Caruso R, Trosko J E
Crit Rev Toxicol. 1985;16(2):157-83. doi: 10.3109/10408448509056269.
Teratogenesis and carcinogenesis share many characteristics, leading to the speculation that they may also share pathogenic mechanisms. Direct intercellular communication mediated by membrane junctions is known to occur between a variety of cells and may play an important role in the control of cell growth and differentiation. Inhibition of junctional communication may be a mechanism common to both teratogenesis and carcinogenesis whereby cells and tissues are diverted from their normal differentiation paths. The multistage model of carcinogenesis predicts that the irreversibly initiated cell is at least partially regulated by the surrounding cells of a tissue, and that the initiated cell remains inactive until stimulated to proliferate by a tumor promotor. Tumor promoters may release the initiated cell from control of the surrounding tissue by interrupting intercellular communication, since many tumor promoters have now been shown to interfere with junctional communication in cultured mammalian cells. Furthermore, many tumorigenic cells have compromised junctional communication abilities. Similarly, it has been reasoned that the cells of an embryo must be able to communicate with each other to define tissue specificity and pattern formation, and to coordinate morphogenetic events. Many studies have chronicled alterations in junctional communication that occur coincident with major developmental events and some studies suggest that junctional communication may be modified at boundaries of morphogenetic fields. A recent in vivo study has provided evidence that inhibition of junctional communication may interfere with embryonic development, and several teratogens are known to interrupt junctional communication in mammalian cells in culture. These observations suggest that inhibition of junctional intercellular communication may be a shared mechanism of carcinogenesis and teratogenesis.
