Role of Inhibition of Intercellular Communication in Carcinogenesis

Abstract

Subsequent to the first morphologic description of the gap junction by Revel and Karnovsky in 1967 (113), a plethora of reports has appeared describing the structure, function and pathologic changes of this plasma membrane structure. The gap junction appears to serve as a conduit for the cell-to-cell exchange of low molecular weight ions and molecules between adjacent cells (intercellular communication). A number of functions have been attributed to intercellular communication including the maintenance of normal cellular homeostasis. Another function that is clearly related to the neoplastic process is the control of cellular growth (81). Yotti, Chang, and Trosko (178) and Murray and Fitzgerald (99), working independently, reported in 1979 that tumor promoting phorbol ester compounds were capable of inhibiting gap junction-mediated intercellular communication between cells in culture. These findings resulted in the hypothesis that tumor promoters stimulate cell proliferation of initiated cells by inhibiting gap junctional intercellular communication in the initiated cells (146).