EMERGENCE OF UNDIFFERENTIATED RAT TRACHEAL CELL CARCINOMAS, BUT NOT SQUAMOUS-CELL CARCINOMAS, IS ASSOCIATED WITH A LOSS OF EXPRESSION OF E-CADHERIN AND OF GAP JUNCTION COMMUNICATION

A series of cells representing normal, non-tumorigenic cell lines, as well as differentiating neoplastic and undifferentiated neoplastic rat tracheal epithelial cell populations were evaluated for their ability to establish homologous and/or heterologous cell-cell gap junction co mmunication in culture. Gap junction communication was evaluated by fl ow cytometric quantitation of the transfer of the fluorescent dye calc ein from a donor to a recipient cell population via gap junctions, The data indicate that normal primary cultures of rat tracheal epithelial cells, as well as non-tumorigenic cell lines and squamous cell carcin omas cell populations, retain the ability to establish both homologous and heterologous gap junction communication. In all cases an average of >48 % of recipient cells had acquired calcein label during a 5-h in terval of co-culture of donor and recipient cells at confluent densiti es, Cells harvested directly from squamous cell carcinoma tumors exhib ited similar levels of cell-tell communication. In contrast, cells giv ing rise to undifferentiated carcinomas, as well as cells harvested fr om undifferentiated carcinomas, exhibited very low levels or no homolo gous or heterologous cell-cell communication, Cell populations exhibit ing distinctly different communication phenotypes were evaluated by No rthern blot analysis for expression of connexins (Cx 26, 32 and 43) an d E-cadherin, Neither communicating nor non-communicating cells expres sed connexin 32, Those cell populations, which established functional gap junctions, expressed E-cadherin as well as connexin 26 and/or 43. In contrast, those cell populations that lacked the ability to communi cate universally lacked expression of E-cadherin, and a quarter also l acked expression of detectable levels of connexin.