GAP JUNCTION FUNCTION AND CANCER

Gap junctions (GJs) provide cell-to-cell communication of essential me tabolites and ions. GJs allow tissues to average responses, clear wast e products, and minimize the effects of xenobiotics by dilution and al lowing steady-state catabolism. Many chemicals can adversely affect th e membrane GJ assembly causing reversible alterations in GJ intercellu lar communication. During toxicity essential metabolites, ions, and re gulators are not shared homeostatically throughout a tissue community. Alterations in metabolic circuits are thought to interrupt organ inte gration. Persistent GJ perturbation can cause chronic effects (e.g., c ancer), and many tumor promoters inhibit GJ intercellular communicatio n. Liver precancerous foci intracommunicate (but at a reduced level) a nd intercommunicate improperly (or not at all) across the foci boundar y to normal cells. In time, foci can become less regulated and more is olated within the tissue. Gjs remain reduced quantitatively in the tum or progression stage and may be qualitatively altered in metastasis si nce connections are made between the primary tumor cells and foreign h ost cells at the secondary metastatic site. Cell sorting and binding m echanisms by the cell adhesion molecules and integrins may also be alt ered at secondary sites. This may allow the relocation of primary tumo r cells and nurturance via GJs at the secondary site.